postmenopausal women with osteoporosis
TRANSCRIPT
FACULTY OF HEALTH AND OCCUPATIONAL STUDIES Department of Public Health and Sport Science
Postmenopausal Women with Osteoporosis
The Effect of Physical Exercise on Markers Linked to Quality of Life
Henrik Gustafsson
2021
Student thesis, Bachelor level, 15 Credits Public Health
Health Promotion through Sustainable Development Research Methods in Public Health II and Thesis writing 30 Credits
FHG800 Supervisors: Francesca Maffei, Sandra A.I. Wright, and Sofia Marini
Head Advisor in the Subject Area of Public Health: Anne-Sofie Hiswåls Examiner: Gloria Macassa
Gustafsson, H. (2020). Postmenopausal women with osteoporosis – The effect of physical
exercise on markers linked to quality of life. Bachelor thesis in Public Health Science.
Department of Public Health and Sport Science. University of Gävle, Sweden.
Abstract
This study has aimed to evaluate how osteoporosis affects the quality of life in
postmenopausal women and to assess the influence of physical exercise on markers for
quality of life in osteoporosis patients. The EQ-5D questionnaire was applied for
evaluation of the markers: Mobility, Self-care, Usual Activities, Pain/Discomfort and
Anxiety/Depression. In collaboration with the University of Bologna, a 6-month exercise
trial of women aged 60-75 with osteoporotic vertebral fractures was analyzed. These
osteoporosis patients were divided into two groups; an exercise group and a control group.
Markers linked to quality of life were compared for the women with osteoporosis with
those of an average female Italian population of similar age. Markers for quality of life,
specifically: Mobility, Usual Activities, Pain/Discomfort and Anxiety/Depression were
significantly lower in the Italian osteoporosis patients than in the average population.
Exercise slightly improved Mobility and Usual Activities for the osteoporosis patients,
but the results did not reach statistical significance.
Keywords: osteoporosis, quality of life, physical exercise, postmenopausal women,
vertebral fractures
Sammanfattning
Denna studie har syftat till att undersöka hur osteoporos påverkar livskvaliteten hos
postmenopausala kvinnor (dvs. efter klimakteriet) och att bedöma påverkan av fysisk
tränings på markörer för livskvalitet hos osteoporospatienter.
Frågeformuläret EQ-5D användes för utvärdering av markörerna: rörlighet, egenvård,
vardagsaktiviteter, smärta/obehag och oro/nedstämdhet. I samarbete med universitet i
Bologna analyserades en 6 månaders träningsstudie av kvinnor i åldrarna 60-75 år med
osteoporotiska ryggradsfrakturer. Dessa osteoporospatienter delades in i två grupper; en
träningsgrupp och en kontrollgrupp. Markörer kopplade till livskvalitet jämfördes för
kvinnor med osteoporos och kvinnor från en italiensk genomsnittspopulation i liknande
ålder. Markörer för livskvalitet, särskilt: rörlighet, vardagsaktiviteter, smärta/obehag och
oro/nedstämdhet var signifikant lägre hos de italienska osteoporospatienterna jämfört
med genomsnittspopulationen. Träning förbättrade rörlighet och vardagsaktiviteter något
för osteoporospatienterna, men resultaten nådde inte statistisk signifikans.
Nyckelord: osteoporos, livskvalitet, fysisk träning, postmenopausala kvinnor,
ryggradsfrakturer
Acknowledgements
Support, patience and extraordinary supervision – without those components, this thesis
would not have been possible to realize. I would like to express my deepest appreciation
to Professor Sandra A. I. Wright, for teaching me valuable research skills. You have
generously given your time, even when you had other commitments simultaneously. I am
also grateful to you for introducing me to Professor Francesca Maffei, at the University
of Bologna. Thanks are due to Prof. Maffei, for her endless patience during all our Zoom
meetings throughout the unusual 2020 year, and for introducing me to the subject of
osteoporosis. I hope I will be able to visit the university campus one day. I would like to
express my sincere gratitude to Sofia Marini and for generously sharing the data and for
valuable suggestions on this thesis. I am honored that I could take part in your study. My
sincere appreciation also goes to Laura Dallolio, for sharing the data and for appreciating
my contribution of analyzing the data. Although not formally my supervisor, Professor
Niclas Olofsson patiently and generously introduced me to statistics and supported me
throughout the data collection. The information became clearer as I evaluated and
processed the data and you made me aware of the complexity of statistics.
I am also owing gratitude to Mia Mårdberg, at the University of Gävle Writing Center,
and librarian Karin Meyer Lundén for replying to my questions. I would also like to
acknowledge the support of Christina Edin and Marie-Louise Holmberg. I truly
appreciate the support I have got from Professor Yuko Okubo, at the University of
California, Berkeley and Stefanie Lazer at the American Psychological Association, for
giving me comprehensive guidance on questions regarding references. I am also thankful
to the physical therapists; Margaret Martin, in Ottawa, for letting me use her video
material, and my brother Alex for putting up with inquires. Kaisori Bellach has been there
by my side with her sincere support even her time was limited. Thank you for your helpful
advice, as always. A special thanks goes to my girlfriend for being patient and supportive
during the thesis project, and to my family for their support and encouragement
throughout my studies.
Table of Contents 1. Introduction ......................................................................................................... 1
1.1 Osteoporosis as a Public Health concern ..................................................................... 1 1.2 Development of Osteoporosis; the Effect of Physical Exercise and Lifestyle ................. 2 1.3 Osteoporosis and Quality of Life ................................................................................. 4
2. Aim of the Study ................................................................................................... 7
3. Research Questions .............................................................................................. 7
4.Methods ................................................................................................................ 8 4.1 Study Design .............................................................................................................. 8 4.2 Selection Criteria ........................................................................................................ 8 4.3 Data Collection and Questionnaire ............................................................................. 8 4.4 Conducting the study ............................................................................................... 14 4.5 Data Analysis ........................................................................................................... 15 4.6 Ethical considerations .............................................................................................. 15
4. Results ............................................................................................................... 17
6. Discussion .......................................................................................................... 22 6.1 Discussion of Results ................................................................................................ 22 6.2 Discussion of Methods ............................................................................................. 26 6.3 Future Research ....................................................................................................... 29
7. Conclusions ........................................................................................................ 30
8. References.......................................................................................................... 31
Preface
During this thesis work, I have understood that the concept of quality of life is complex,
i.e. that it can refer to different things, depending on the personal values of an individual.
Although its immediate connotation appears to be related to health, quality of life may,
in fact, not necessarily always indicate the same as what we consider as "healthy".
Osteoporosis affects physical as well as psychological health. To feel neglected may
perhaps be conceived as even worse to the individual than the physical trauma of a
fracture that osteoporosis often leads to, and there could be countless unrecorded data on
the psychological costs of the disease.
While searching the literature, it did not take long to understand that patients with
osteoporotic fractures have not been prioritized, which Cosman et al., (2014) highlighted,
by stating that in the U.S., many individuals with osteoporotic fractures do not get a
diagnosis or have received proper therapies. In Sweden, vertebral fractures caused more
morbidity than hip fractures up to age 75 (Kanis et al. 2004). Despite the high prevalence
of osteoporotic fractures, Swedish physicians reported that the national health care system
ordered staff to set low priority to osteoporosis. Consequently, only about 14% of the
patients received bone-specific aid after a fracture (Salminen et al., 2019). This indicates
that the problem could worsen and lead to side effects, such as repeated fractures. The
women in this study have had one or several fractures due to osteoporosis. In fact, a major
risk factor for obtaining a fracture is existing, previous fractures (Cipriani et al., 2018).
These may lead to chronic pain, and in some cases, fatality. For instance, several studies
reported a higher risk for mortality in patients with vertebral fractures (Cauley et al., 2000;
Hallberg et al., 2004); it was even nine times higher than in the general population,
according to a Polish review by Haczynski and Jakimiuk (2001). In the present study, the
effect of osteoporosis on quality of life was investigated.
With the burden on society that osteoporosis causes, bone health investment is essential
and should also be prioritized, due to the risk of comorbidities after a fracture. It may
require health policy planners to be rationally open-minded, since immediate evidence
seldom occurs, for example from exercise trials. Research on long-term effects of
physical exercise and awareness of the influence of diet and drugs on exercise may be
suitable for future measures, as reviewed by Benedetti et al. (2018). In the present thesis,
the influence of exercise on markers linked to quality of life was investigated. A positive
aspect of physical exercise is that it can be carried out at home, without posing an
economic burden on the patient (Koevska et al., 2019). Accordingly, physical exercise is
excellent for disease prevention, also for those with limited financial means, being of help
to the public health and the individual. Thus, it is important that funding is made available
for these types of studies and that future research in osteoporosis is encouraged.
The United Nations General Assembly (2015) stated the importance of promoting
physical and mental health in individuals with non-communicable diseases (NCDs),
including osteoporosis. Recently, a report of NCDs showed a decrease in fracture
assessment of osteoporosis patients in many countries during the COVID-19 pandemic
(McCloskey et al., 2020). Early diagnosis is crucial since osteoporosis later can create a
heavy burden on the public health systems. It should not be neglected due to the current
challenges of a pandemic. Social distancing with people working or studying from home
can lead to increasing sedentary behavior and this may lead to a second pandemic of
osteoporosis. This may be a global problem but especially in the northern hemisphere
during the cold season, with lack of natural vitamin D from the sun, which is needed for
healthy bones.
As mentioned earlier, no symptoms appear for over half of the patients with vertebral
fractures (Lentle et al., 2007). Therefore, not only the osteoporosis condition may go
undiagnosed but a person with a fracture may also not receive medical care, which in turn
may lead to personal trauma and a subsequent burden on the primary health care (Gold et
al., 2019). This is costly also to the families of patients since it affects physical and mental
health, which is socially and financially unsustainable. The costs for health care systems
are massive when osteoporosis has set in. Thus, the public health system needs to
cooperate with experts in osteoporosis to remain competent on strategies that are efficient,
safe, feasible and effective, including physical therapy, as both primary and secondary
measures of prevention of osteoporosis; these strategies may also help to speed up the
healing of fractures. This thesis was based on a collaborative research trial between the
University of Bologna, health care practitioners, and osteoporosis patients. During the
present study, I have concluded that cooperation among researchers and patients to
prevent the impact of fragility fractures, such as comorbidities, needs to become a top
priority for health authorities. Osteoporosis is currently a hot topic, and how it affects
different markers of quality of life is what mostly made me consider to investigate this
subject. While the pandemic of COVID-19 is going on, another pandemic of osteoporosis
is silently moving forward. Bone fragility is so common that almost everyone knows
another person with osteoporosis, or someone that had a fracture. Therefore, we should
ask ourselves why this may be, and what we can do. Health authorities need to implement
efficient risk assessment of fractures to promote favorable choices of lifestyle, which
could contribute to promoting quality of life.
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1. Introduction
1.1 Osteoporosis as a Public Health concern
Osteoporosis is defined as bone fragility or "porous bone”. It is a chronic, degenerative
disease of the skeleton and a major public health problem that results in decreased bone
strength, which can increase the risk of bone fracture (Hernlund et al., 2013; National
Institute of Arthritis and Musculoskeletal and Skin Diseases, n.d.). Osteoporosis is
especially prevalent among elderly women. A correlation between osteoporosis and the
onset of menopause was observed already in the 1960s (Tella & Gallagher, 2014). Low
estrogen levels after menopause are believed to cause bone loss and lead to osteoporosis
(Agostini et al., 2018). Hundreds of millions of people are affected worldwide and the
prevalence is increasing (Reginster & Burlet, 2006; Hernlund et al., 2013). In people who
are 50 years of age and older, approximately one in two women and one in four men will
have a fracture caused by osteoporosis (National Osteoporosis Foundation, 2020). A U.S.
survey of postmenopausal women from 2000 to 2011 showed that the annual cost due to
hospitalization for osteoporotic fractures was higher than for breast cancer, myocardial
infarction, or stroke (Singer et al., 2015). A report on the medical and economic burden
in the European Union showed that around 22 million women and 5.5 million men had
osteoporosis in 2010. It resulted in roughly 3.5 million fractures. The annual cost of
fractures caused by osteoporosis was approximately EUR 37 billion and has been
predicted to increase by 25% by 2025. However, most persons in Sweden who are
affected by or at risk for an osteoporotic fracture do not receive proper treatment. Instead,
fewer persons are receiving treatment than previously (Hernlund et al., 2013). Fractures
appear after different levels of trauma but until a fracture occurs, osteoporosis is a silent
disorder (Cosman et al., 2014; Lentle et al., 2007). The presence of vertebral fractures,
i.e. fractures localized to the vertebrae of the spine, is widely recognized as an indication
of osteoporosis. These fractures negatively influence physical function, leading to limited
mobility (Borgström et al., 2005; Recknor et al., 2013; Koevska et al., 2019). As reviewed
by Madureira et al. (2012), vertebral fractures may reduce quality of life through lumbar
back pain and comorbidities, such as reduced functions of the heart, lungs and urinary
system. The European Prospective Osteoporosis Study found that incidence rates of
vertebral fractures were higher in Sweden than in any other European country (Felsenberg
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et al., 2002). Moreover, osteoporosis and fractures are also issues in Southern Europe.
More than half of the Italian women over the age of 50 had osteoporosis, according to
Cipriani et al. (2018).
Longevity and osteoporosis
Bone-related disorders can be understood through the prevalence of longevity in a
population since bone mineral density (BMD) decreases with old age. Osteoporosis
constitutes a global health problem, since the median age is increasing in the world, due
to low fertility and increased longevity. Life expectancy is especially high in developed
countries, and Europe has the oldest median age in the world. The fastest-growing
population group is people over the age of 60. By 2050, in developed countries, the
number of elderly is estimated to be twice as high as the number of children (United
Nations, 2011). This gives an idea about how urbanized nations will be affected by bone
fragility, due to aging populations. After all, quality of life is an important component of
longevity and longevity affects the quality of life.
1.2 Development of Osteoporosis; the Effect of Physical Exercise and
Lifestyle
Aging leads to a lower BMD (osteopenia) and muscular density (sarcopenia) (dos Santos
Silva et al., 2019). High BMD is essential for preventing osteoporosis and it can depend
on genetic predisposition, such as ethnicity (Whedon, 1984; Smith, 1985). Measuring
bone density is part of the regular risk evaluation for preventing osteoporosis-related
fractures (Cummings et al., 1993; Marshall et al., 1996). However, there is limited
information regarding facture incident proportions in postmenopausal women with either
low or regular BMD (Cranney et al., 2007).
Physical exercise is an effective way to build up bone mass, and it contributes to
osteogenesis; the formation and maintenance of the bones, as reviewed by Benedetti et
al. (2018). Findings suggest that physical exercise prevents osteoporosis through
counteracting and slowing down the loss of bone from the lumbar vertebrae at the lower
back spine (Krølner et al., 1983). In fact, exercise is believed to be the most fundamental
non-pharmacological treatment for facilitating the healing of fall-related fractures and
delaying the outbreak of osteoporosis (Agostini et al., 2018). Emphasis on exercise is of
3
importance, since decreasing physical activity among elderly is a contributing factor as
to why they are more prone to osteoporosis (ibid).
Physical exercise can improve overall quality of life. It may contribute to improving self-
esteem and social life among women with osteoporosis, as seen in a Macedonian study
(Koevska et al., 2019). There are different types of exercise that lead to vitalization.
Resistance strength training of the lower limbs strengthens the femoral neck. However,
for patients with disorders of the spine (vertebrae), multicomponent exercises appear to
be the most effective. These include a combination of "weight-bearing activities", such
as Tai Chi, walking, jogging, and stair climbing with resistance and strength training with
weights, as reviewed by Benedetti et al. (2018). Recommendations that has been proven
helpful for women with vertebral fracture include exercises for strengthening the back,
upper and lower extremities, combined with balance training and should be individually
applied (Dusdal et al., 2011; Giangregorio et al., 2013). Evidence is limited regarding the
effects of physical function on quality of life in patients with vertebral fractures, which
was reviewed by Gibbs et al. (2019). As reported by Benedetti et al. (2018), there are
three areas of physical exercise for osteoporosis patients:
1. Weight-bearing aerobic exercises
2. Strength and resistance exercise
3. Balance training
Exercises suited to individuals with vertebral fractures may consist of modified trunk and
lower extremity muscle strengthening, exercises directed to correction of posture,
challenging balance practices combined, and aerobic physical activity with moderate
intensity, according to Gibbs et al. (2019). An important discrepancy has to be made about
different types of physical exercise. Exercise may prevent osteoporosis but safe exercise
is crucial for individuals with fractures. As explained by Sinaki (2012), exercise may be
helpful to manage osteoporosis, but could even be harmful to individuals with vertebral
fracture, if not conducted properly. Spine-flexing activities, including twisting and
bending of the spine, such as in yoga or Pilates, have been shown to cause vertebral
fractures and should be avoided (Sinaki., 2013).
Overall, the population in modern society is successively becoming more sedentary
(Owen et al., 2020). Some risk factors for morbidity include physical inactivity, such as
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the number of individuals older than 15 years of age, who are classified as moderately
physically active for less than half an hour per week. Physical activity has predominantly
decreased in high-income countries. In 2008, almost every second woman in high-income
countries was considered physically inactive (World Health Organization, 2011). In any
case, it is important to be physically active at all ages (Kannus, 1999).
1.3 Osteoporosis and Quality of Life
Health-related quality of life, or simply quality of life, defines the well-being of an
individual. It includes environmental and financial aspects in addition to the general
health status of a person. The term has been relevant since 1948, after the humanitarian
tragedies of World War II, when the World Health Organization defined health as more
than the absence of disease. It has been a widely used term in the MEDLINE database
since the 1970s, as reviewed by Testa and Simonson (1996). To have a sense of coherence
is necessary for quality of life in osteoporosis patients. A study found social support and
socioeconomic factors to speed recovery and decrease mortality after hip fracture. Over
time, this treatment also had positive effects such as pain relief, shorter hospitalization,
and improved quality of life (Auais et al., 2019). Social support was mentioned as an
important factor for physical function also by Kerr et al. (2017). Conversely, disability
may restrict participation in society.
Instruments for measuring health-related quality of life
Quality of life cannot be clinically measured, since it is a subjective experience.
Therefore, self-assessment through measurement scales are often used. Even though
quality of life is commonly associated with social sciences, it is of relevance for clinical
studies, for example in estimating the cost-effectiveness of medical interventions (Testa
& Simonson, 1996). Since quality of life is multidimensional, the instruments need to
include several dimensions (Lydick et al., 1997). Many different questionnaires exist to
measure the quality of life in osteoporotic patients through patient-reported outcome. Two
of the most commonly used are the EQ-5D and the QUALEFFO-41. EQ-5D is a generic
health-related quality of life questionnaire, while QUALEFFO-41 is a disease-specific
questionnaire for measuring the quality of life in patients with vertebral fractures (van
Schoor et al., 2006).
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The EuroQol Group, a global research organization, has developed the EQ-5D, a
standardized questionnaire for the measurement of health-related quality of life (Rabin &
de Charro, 2001). Markers used to measure the effect of osteoporosis on quality of life
include Mobility, Self-care, Usual Activities, Anxiety/Depression and Pain/Discomfort,
which all contribute to physical functions, psycho-social state, and well-being. The EQ-
5D is available in three versions: EQ-5D-3L, EQ-5D-5L and the EQ-5D-Y. A list of
terminology is accessible via the EuroQol website:
https://euroqol.org/support/terminology/ (Brooks et al., 2020). The EQ-5D is utilized in
clinical settings, clinical trials and population studies worldwide. The EQ-5D-3L is
translated into 180 different languages. Each of the adapted versions comes with a
translation protocol that conforms to the International guidelines, which guarantee that
these are equal to the original version in English, as stated in the EQ-5D-3L User Guide
(EuroQol Research Foundation, 2018).
The effect of vertebral fractures on quality of life
Vertebral fractures can cause chronic pain and disability, which reduce the quality of life
even after healing (Hallberg et al., 2004; Suzuki et al., 2010; Jung et al., 2017; Gold et
al., 2019). A fracture leads to a lower quality of life through impaired social and physical
function in postmenopausal women with osteoporosis (Fechtenbaum et al., 2005). After
a fracture, increased fear of falling is common in the affected individual. Fear of falling
and dependency on others after a fracture often makes the patient more inactive, which
increases the osteoporotic condition. In fact, fear of falling has a serious impact on the
quality of life in women with osteoporosis (Lydick et al., 1996). This sequence of events
manifests itself as a vicious circle, depicted in Figure 1 (Kerr et al., 2017).
6
Figure 1. The vicious circle of deterioration during osteoporosis. The figure is adapted from the original by Kerr et al. (2017).
Figure 1 shows how the different aspects of osteoporosis affect each other. Decreased
physical performance may lead to loss of bone and muscle, which in turn may lead to
fractures; and fractures are usually painful. The pain is likely to cause a decline in physical
performance – and that is where everything started. The result is a vicious circle, which
affects the quality of life of the osteoporosis patient.
After a fracture, the osteoporosis patient may have a reduction or absence of ability to
perform daily tasks, i.e. Usual Activities. Some examples include the ability to shower,
pick up things, manage to get up from chairs or seats, etc. This is often due to decreased
Mobility and Pain/Discomfort, but also fear of falling, which may present itself as
Anxiety/Depression. Self-care may thus be even more difficult after a fracture for the
elderly. Self-care is defined as the ability to take care of ones personal hygiene and
independently sustaining oneself (Brooks et al., 2003). As seen in Figure 1, fractures have
an impact both physically and psychologically – it has an especially large negative
psychosocial impact. The consequences of a fracture are worse for the elderly, because
of the likelihood of social isolation and because of a general deterioration in physical
health (Kerr et al., 2017). Markers used to measure the effect of osteoporosis on quality
of life are listed in the middle of Figure 1. These markers are important for planning
integrated therapeutic strategies for the treatment of individuals affected by osteoporosis
(Rabin & de Charro, 2001; Marini et al., 2019). To ultimately break the vicious circle
7
(Fig 1), and prevent and counteract osteoporosis, a regular physical exercise routine may
serve as a final solution (Kannus et al., 1995).
The present study focuses on postmenopausal women, since they are particularly prone
to osteoporosis and affected by it, to such a degree that osteoporosis in these women
represents a serious global public health problem. There is evidence to suggest that
physical exercise may help women to obtain a better quality of life, even if they start
exercising later in life (Choi, 2013).
2. Aim of the Study
To investigate the impact of physical exercise on health and wellbeing and to evaluate
markers linked to quality of life among Italian postmenopausal women with osteoporosis
and a history of vertebral fractures.
3. Research Questions
• How can osteoporosis interfere with quality of life among Italian
postmenopausal women?
• Can physical exercise influence markers linked to quality of life (Mobility,
Usual Activities, Self-care, Pain/Discomfort and Anxiety/Depression) among
osteoporotic patients?
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4.Methods
4.1 Study Design The research was part of a quasi-experimental controlled 6-month trial, with non-random
assignment. The study was non-randomized, because the selection of participants was
based on voluntary participation in the exercise program. Forty women participated in the
study. The studied population was classified into two groups: Adapted Physical Exercise
Group (22 subjects) and a Control Group (18 subjects). The Control Group did not change
their lifestyle during the six months. The Exercise Group however, followed a specific,
regular exercise program, adapted for persons suffering from osteoporosis (Marini et al.,
2019).
Perceived quality of life among the participating women at the beginning of the exercise
study was compared to that of an average Italian population. The population consisted of
individuals of similar age and gender (Table 1).
4.2 Selection Criteria To be included in the study, the participants had to be 60- to 75-year-old postmenopausal
females from the city of Bologna, Italy. The studied population was recruited by the
Internal Medicine Unit at Sant'Orsola Malpighi University Hospital in Bologna during
daily outpatient activity. All of the participating women lived at home. They had
confirmed osteoporosis, verified by dual-energy X-ray absorptiometry (DXA), and a
history of at least one vertebral fracture. Most of them followed drug therapy for
osteoporosis. The pharmacological administration was constant throughout the study.
This thesis is utilizing some data from of a large study that never were analyzed or
published previously. They form the basis for the present thesis.
4.3 Data Collection and Questionnaire
The collection of data was based on patient-reported outcomes through the EQ-5D-3L
questionnaire, since the study that provided the data applied this version (EuroQol
9
Research Foundation, 2018; Marini et al., 2019). Included were questions regarding five
markers related to quality of life: Mobility, Self-care, Usual Activities, Pain/Discomfort
and Anxiety/Depression. There was also a visual analog scale; EQ VAS, where each
woman could indicate her self-assessed overall state of health.
The EQ-5D-3L questionnaire estimates the state of health in three ways: 1) by the EQ-
5D-3L descriptive system of five dimensions (markers) linked to quality of life at three
levels, 2) by the EQ VAS (scale measuring overall quality of life), 3) by the EQ-5D index
value (EuroQol Research Foundation, 2018).
The EuroQol Research Foundation has provided the following demo version (sample) of
the EQ-5D-3L questionnaire seen on the next page:
10
11
12
Figure 2. The EQ-5D-3L questionnaire (sample version) shown for illustrating purposes.
© EuroQol Research Foundation. Reproduced by permission of EuroQol Research Foundation.
EQ-5DTM is a trade mark of the EuroQol Research Foundation. Reproduction of this version is not
allowed. For reproduction, use or modification of the EQ-5D (any version), please register your study by
using the online EQ registration page: www.euroqol.org.
13
1. Application of the EQ-5D-3L to estimate the state of health
The questionnaires, which were in paper format, were given to the osteoporosis patients.
The patients were asked to tick one of three boxes next to each of the five markers linked
to quality of life. There were three levels to choose from when assessing health: 1. no
problem, 2. some problems, 3. extreme problems.
When these levels were combined with the markers for quality of life, a distinctive health
state for each individual was created.
The EQ-5D-3L has 5 dimensions (markers) with 3 levels. The five markers create a code
of five numbers from the chosen levels of 1, 2, 3. For example, a health state of 12231
would indicate no perceived problems with Mobility, some with Self-care and Usual
Activities, extreme problems with Pain/Discomfort and none with Anxiety/Depression.
On the other hand, 11111 would indicate no perceived problems with any of the five
markers (EuroQol Research Foundation, 2018). Each patient received a personal health
profile, created by treatments and visits. The distribution of the responses of each marker
were recorded in a table and percentages were calculated. The five number digits also
contributed to a summary EQ-5D index, which is described below.
2. Imagined and self-assessed state of health through a visual analog scale
The EQ VAS allowed the osteoporosis patients to estimate their self-rated health by
placing a cross on a scale of 0 to 100, where 0 meant "worst imaginable health" and 100
meant "best imaginable health (Marini et al., 2019; Rabin & de Charro, 2001). The
percentage estimated health level was recorded by each patient as a number in a box on
the same page (The EuroQol Research Foundation, 2018).
3. The summary EQ-5D index value
Summarized data from (step one) are automatically created by the program, thus
generating the EQ-5D index, which is a measure of the level of health of the studied
population. All the values or weights attached to the markers were based on societal
standards of the country-specific version. That is, the average population of a country has
given values for VAS-valuation or time-trade-off. The EQ-5D index value ranges from -
0.171 to 1. An individual with a score of 0 was considered to be dead, whereas an
individual with a score of 1 experienced the best possible health. To calculate the index,
the appropriate country values can be deducted from the value of full health, which is
11111. The calculation of quality-adjusted life years is applied through this index and
14
used for economic assessment in health interventions (EuroQol Research Foundation,
2018).
4.4 Conducting the study
This study was carried out in collaboration with the Department for Life Quality Studies
(Rimini Campus) and the Department of Biomedical and Neuromotor Science (Bologna
Campus) of the University of Bologna in the framework of an Erasmus+ mobility.
The data were kindly provided by Francesca Maffei, Sofia Marini and Laura Dallolio
through a pilot study conducted by the University of Bologna (Department of Biomedical
and Neuromotor Sciences and Department for Life Quality Studies), in co-operation with
the Bologna University Hospital Authority St. Orsola-Malpighi Polyclinic in Bologna.
The pilot study, among the outcome assessments, applied the EQ-5D-3L questionnaire
for the data collection relatively to the health-related quality of life domain, and therefore
the present thesis applied the same method using the data collected but not yet described
by Marini et al. study (2019). The participants completed the questionnaire at the
beginning and the end of the study. The answers for the two-time points were called pre-
intervention and post-intervention, respectively. The data were collected by trained and
blinded assessors, with the supervision of Sofia Marini and the research team. However,
the study could not be considered randomized, since the patients participated in the
exercise program on a voluntary basis. All the participants in the study confirmed at the
outset in writing their informed consent to participate in the study (Marini et al., 2019).
The participants of the Control Group were recommended to proceed with their current
lifestyle. The Exercise Group participated in a one-hour long training session twice a
week, administered at specific gym, by graduates with Master of Science Degrees in
Sciences and Techniques of Preventive and Adapted Physical Activity of the University
of Bologna. Each training session started with a 15 minutes’ warm-up of cardio-
respiratory conditioning, coordination and mobility exercises and balance training. The
larger part of the session was based on weight-free strengthening exercises and finally,
every session ended with a ten-minute cool-down. Exercises that could lead to vertebral
fractures were deliberately excluded from the training program, particularly those related
to spinal flexion and twist. Simple materials, such as elastic bands, mats and sponge balls
15
were used at every session. The exercise intervention lasted for a period of six months
(Marini et al., 2019).
4.5 Data Analysis The average Italian population, which consisted of 247 women in the age range of 65 to
74 years old was chosen as a reference population for comparison to the osteoporosis
patients. The data of the average Italian population were extracted from the book: Self-
Reported Population Health: An International Perspective based on EQ-5D (Szende et
al., 2014, pp. 101-105). The parametric, two proportion Z-test was used to analyze EQ-
5D questionnaires regarding quality of life comparisons between the osteoporosis patients
and the average Italian population. The Z-test allows you to compare two proportions to
see if they are the same. The null hypothesis (H0) for the test was that proportions were
the same for the average population as for the osteoporosis patients.
Since the sample size of the participants in the exercise program was small and not
normally distributed, a non-parametric Wilcoxon Signed-Rank test was used when
comparing the Exercise group with the Control group, before and after the intervention.
Lastly, a Mann-Whitney U test was used, to compare independent samples of the Exercise
Group to those of the Control Group. Results with p values lower than 0.05 were
considered significant. The analysis was carried out through the IBM SPSS Statistics
software (IBM Corporation, 2016).
4.6 Ethical considerations In 2004, an act about the research involving human subjects passed legislation. All
research involving human subjects must be given the permission by an ethics committee.
According to the United Nations Declaration of Human Rights, all individuals have the
right to integrity (Swedish Research Council, 2017). Some women did not want to be part
of the Exercise Group, for different reasons. Therefore, the patients included in the
Exercise Group, voluntarily opted to take part in the physical exercise program. Freedom
of choice is an important ethical aspect. The fact that patients freely could choose to
participate in the program could have had a positive effect on their willingness to adhere
to the exercise program. It also meant that the osteoporosis patients were not randomly
16
distributed over the two groups (Marini et al., 2019). The Independent Ethics Committee,
Azienda Ospedaliera di Bologna, Policlinico S. Orsola-Malpighi approved the study (ref.
143/2014/U/Sper; Marini et al., 2019).
17
4. Results
A group of osteoporosis patients consisting of 40 postmenopausal women was compared
to a similar group of the average Italian population with regard to their perception of
quality of life. The objective was to determine if osteoporosis could affect markers linked
to quality of life. The EQ-5D index value was significantly lower for the osteoporosis
patients, which indicated that osteoporosis had a negative impact on the experienced
quality of life. The markers that significantly differed across the two populations were:
Mobility, Usual Activities, Pain/Discomfort and Anxiety/Depression. Self-care was the
only marker that did not significantly differ between the osteoporosis patients and the
average Italian population (Table 1).
18
Table 1. Markers for quality of life at start of the study - a comparison between Italian osteoporosis patients and a gender and age-controlled average Italian population. Significant differences are highlighted in bold (p ≤ 0.05)
MARKER FOR QUALITY OF LIFE (3 levels for health evaluation by EQ-5D-3L1)
OSTEOPOROSIS PATIENTS n = 40
n (%)
AVERAGE ITALIAN POPULATION n = 247
n (%)
p value
MOBILITY
1. NO PROBLEM 2. SOME PROBLEMS 3. CONFINED TO BED
25 (62.5) 15 (37.5) 0 (0.0)
175 (68.5) 71 (31.2) 1 (0.3)
0.720 0.001 0.690
SELF-CARE
1. NO PROBLEM 2. SOME PROBLEMS 3. UNABLE TO WASH OR DRESS
35 (87.5) 5 (12.5) 0 (0.0
220 (88.1) 24 (10.9) 3 (1.0)
0.770 0.590 0.480
USUAL ACTIVITES3 1. NO PROBLEM 2. SOME PROBLEMS 3. UNABLE TO PERFORM
22 (55.0) 18 (45.0) 0 (0.0)
187 (73.8) 54 (23.9) 6 (2.3)
0.006 0.002 0.320
PAIN/DISCOMFORT 1. NO PROBLEM 2. MODERATE PROBLEMS 3. EXTREME
8 (20.0) 31 (77.5) 1 (2.5)
114 (44.6) 117 (48.1) 16 (7.3)
0.002 0.001 0.320
ANXIETY/DEPRESSION 1. NO PROBLEM 2. MODERATE PROBLEMS 3. EXTREME PROBLEMS
22 (55,0) 16 (40,0) 2 (5.0)
200 (79,7) 43 (18,8) 4 (1.5)
0.001 0.001 0.170
PARAMETER
OSTEOPOROSIS PATIENTS MEAN (SE)
AVERAGE ITALIAN POPULATION MEAN (SE)
p value
EQ-5D INDEX4 0.607 (0.049) 0.783 (0.015) 0.001
EQ VAS SCORE5 67.8 (2.6) 65.3 (1.5) 0.410
1EQ-5D-3L; Descriptive system of the markers linked to quality of life with 3 levels of self-experienced health, where 1 is no problem, 2 signifies some- or moderate problems and 3 indicates extreme problems (Rabin & de Charro, 2001). 2A two proportion Z-test was used to compare the two populations and obtain a probability of results (p value) 3Ability to participate in leisure activities, work, studies, housework, etc. It does not include the use of public transportation, car, bicycle, etc. (Brooks et al., 2003)
4Mean (SE) score of the EQ-5D composes the EQ-5D index value, in which the levels are: 1 (full health), 0 (a state as in being dead) and below 0, a state worse than being dead (ibid; EuroQol Research Foundation 2018; Patrick et al., 1994)
5Mean score for EQ VAS (%)
19
The second part of the study consisted of an evaluation of an intervention within the group
of the same 40 postmenopausal women, which were affected by osteoporosis and living
in Bologna, Italy. The study assessed the effect of physical exercise on markers of quality
of life among these patients (Table 2).
Table 2. Inter-group comparison of 40 osteoporosis patients between an exercise group and a control group, pre- and post-intervention
MARKER FOR QUALITY OF LIFE
EXERCISE GROUP
n = 22
CONTROLGROUP
n = 18
EXERCISE GROUP n = 22
CONTROLGROUP n = 18
Pre-intervention
Post-intervention
Median (range) p value1 Median (range) p value
MOBILITY 1.5 (1) 1.0 (1) 0.096 1.0 (1) 1.0 (1) 1.000
SELF-CARE 1.0 (0) 1.0 (1) 0.180 1.0 (1) 1.0 (1) 0.968
USUAL ACTIVITES2 2.0 (1) 1.0 (1) 0.262 1.0 (1) 1.0 (1) 0.199
PAIN/ DISCOMFORT 2.0 (2) 2.0 (2) 0.697 2.0 (1) 2.0 (1) 0.717
ANXIETY/ DEPRESSION 2.0 (2) 2.0 (2) 0.199 2.0 (1) 2.0 (1) 0.132
EXERCISE GROUP
CONTROLGROUP
EXERCISE GROUP
CONTROLGROUP
PARAMETER Mean (SE) p value Mean (SE) p value
EQ-5D INDEX 0.53 (1.46) 0.68 (0.81) 0.095 0.62 (0.92) 0.74 (0.81) 0.694
EQ VAS 68 (70) 72 (60) 0.251 70 (75) 70 (70) 0.381
1Medians and ranges are presented with p values from an independent sample of a Mann-Whitney U Test
2Ability to participate in leisure activities, work, studies, housework etc. It does not include usage of public transportation, car, bicycle etc. (Brooks et al., 2003)
3Mean (SE) score of the EQ-5D composes the EQ-5D index value, in which the levels are: 1 (full health), 0 (a state as in being dead) and below 0, a state worse than being dead (ibid; EuroQol Research Foundation 2018; Patrick et al., 1994) 4 Mean score for EQ VAS (%)
20
Table 2 shows a comparison between the Exercise Group and the Control Group at the
beginning (pre) and the end of (post) intervention. The Mann-Whitney U test showed that
the Exercise Group experienced more problems with Mobility than the Control Group at
the beginning of the study. At the end of the intervention, the Exercise Group showed the
same value as the Control Group for Mobility.
The Exercise Group also experienced more problems in performing Usual Activities at
the beginning of the intervention compared to the Control Group. At the end of the
intervention, the Exercise Group showed the same value as the Control Group for Usual
Activities.
Comparisons within each of the groups
The Exercise Group and the Control Group were also compared internally over time, in
the beginning and at the end of the intervention, to see how physical exercise could have
affected the markers linked to quality of life. The Exercise Group tended to experience
fewer problems with Mobility post-intervention as compared to pre-intervention. The
Exercise Group also tended to experience an improvement in performing Usual Activities
post-intervention, as compared to pre-intervention. However, the differences observed
did not reach statistical significance (Table 3).
21
Table 3. Intra-group comparison of 40 osteoporosis patients within an exercise group and a control group through repeated measures, pre and post intervention
MARKER FOR QUALITY OF LIFE
EXERCISE GROUP
n = 22
CONTROL GROUP
n = 18
Median (range)
Median (range
Pre Post p value1 Pre Post p value
MOBILITY 1.5 (1) 1.0 (1) 0.096 1.0 (1) 1.0 (1) 1.000
SELF-CARE 1.0 (1) 1.0 (1) 0.180 1.0 (1) 1.0(1) 1.000
USUAL ACTIVITES2 2.0 (1) 1.0 (1) 0.257 1.0 (1) 1.0(1) 0.083
PAIN/ DISCOMFORT 2.0 (2) 2.0 (2) 0.608 2.0 (1) 2.0 (1) 0.564
ANXIETY/ DEPRESSION 2.0 (2) 2.0 (2) 0.317 2.0 (1) 2.0 (1) 0.317
PARAMETER
EXERCISE GROUP CONTROL GROUP
Mean (SE)
p value Mean (SE) p value
EQ-5D INDEX
0.53 (1.4) 0.64 (0.92) 0.224 0.68 (0.81) 0.74 (0.81) 0.694
EQ VAS 68 (70) 70 (75) 0.126 72 (60) 70 (70) 0.503
1Medians and ranges are presented with p values of a Wilcoxon paired repeated measures test
2Ability to participate in leisure activities, work, studies, housework etc. It does not include usage of public transportation, car, bicycle etc. (Brooks et al., 2003)
3 Mean (SE) score of the EQ-5D composes the EQ-5D index value, in which the levels are: 1 (full health), 0 (a state as in being dead) and below 0, a state worse than being dead (ibid; EuroQol Research Foundation 2018; Patrick et al., 1994) 4 Mean score for EQ VAS (%)
22
6. Discussion 6.1 Discussion of Results
The results showed that the osteoporosis patients experienced an overall lower quality of
life than the average Italian population. Osteoporosis seemed to cause lower quality of
life particularly as regards Mobility, Usual Activities, Pain/Discomfort and
Anxiety/Depression. These findings agree with studies of others (Gold et al., 2019,
Silverman et al., 2001). For example, a Korean study of 196 osteoporosis patients reported
similar trends for markers linked to quality of life (Jung et al., 2017). Just as in the present
study, it examined the impact of osteoporotic vertebral fractures on quality of life, through
the EQ-5D questionnaire. A comparison to a reference population was also made, which
concluded that osteoporosis significantly reduced quality of life.
Regarding Mobility, a greater proportion of the osteoporosis patients in the present study
experienced some problems (37.5%) as compared to the average Italian population
(31.2%). The impact of osteoporosis on the Mobility marker was also significant in the
Korean study (Jung et al., 2017). Other studies confirm these results; Silverman et al.,
2001) reported significantly lower physical function in postmenopausal women with
osteoporotic vertebral fractures; A Norwegian study showed that pain caused by vertebral
fractures mainly affected Mobility through decreased walking speed (Stanghelle et al.,
2019). Not only Pain/Discomfort due to a fracture would make it difficult to walk, but
also the psychological impact from the fear of falling, which can lead to the belief that
one small mistake can cause a new fracture. This may in turn lead to social isolation and
a sedentary lifestyle. Thus, it will decrease Mobility further and similarly affect Usual
Activities; both events render the patient less independent. In the present study, almost
half (45%) of the osteoporosis patients reported some problems in performing Usual
Activities, which agrees with findings by Jung et al. (2017). Moreover, there was a higher
percentage of osteoporosis patients that experienced Pain/Discomfort as compared to the
average Italian population. Only 20% of the patients reported no Pain/Discomfort. Studies
on vertebral fractures agree with these results. An Australian study of persons with low
bone mass (osteoporosis and/or osteopenia), reported Pain/Discomfort as the marker that
was most negatively affected (Gandham et al., 2019). Numerous studies have reported
the correlation between vertebral fractures and pain, as reviewed by Silverman et al.
23
(2001) and Koevska et al. (2019). Osteoporosis is generally not painful, but it increases
the risk of obtaining a fracture. During a fracture acute pain may occur, which can cause
persistent Pain/Discomfort (National Health Service, 2019). In the present study, all the
patients were affected by vertebral fractures, which may have resulted in chronic pain.
Consequently, Pain/Discomfort significantly affected their quality of life, as seen in Table
1. The individual that has suffered a personal trauma and ensuing Pain/Discomfort may
become more careful, due to fear of falling, thus getting habituated to avoiding Usual
Activities, which also lowers his/her Mobility. A low self-confidence in physical ability
and changed body image may cause depression, thus possibly resulting in a change in
Anxiety/Depression. Depression can cause social isolation, which leads to further
depression and lack of motivation, which in turn can result in the avoidance of physical
exercise, and further loss of bone strength ensues (Kerr et al., 2017). A slight negative
trend for Anxiety/Depression was seen in the osteoporosis patients as compared to the
average Italian population, which agrees with the Korean study, in which a significantly
larger proportion of osteoporosis patients experienced Anxiety/Depression as compared
to the reference population (Jung et al., 2017). The psycho-social impact of osteoporosis,
which results in Anxiety/Depression has been thoroughly reviewed (Gold, 1996;
Silverman et al., 2001; Kerr et al., 2017). As described by Gold (1996), vertebral fractures
cause psychological disorders, such as anxiety, depression or bad self-esteem. These
complex issues are difficult to differentiate by using the EQ-5D-3L, which measures
Anxiety/Depression as a single marker. In the present study, Self-care was the only
marker that was not significantly affected by osteoporosis, which agreed with the results
of Gandham et al. (2019). The reasons for this will be addressed in the section entitled:
Discussion of Methods.
An exercise program, which had specifically been adapted for women with osteoporosis
was evaluated in this study. The effect of exercise on the overall quality of life was not
conclusive, in part due to the small sample size in combination with the blunt EQ-5D-3L
instrument, which together generated a large standard error. The EQ-5D index value
tended to increase at the end of the intervention period (after six months), which indicated
that physical exercise could have slightly improved the quality of life for women with
osteoporosis. At the end of the study, it appeared as if the Exercise Group had improved
their performance of Usual Activities, from 2.0 to 1.0 (p = 0.083). These results were not
significant. However, a similar study demonstrated significant improvement of quality of
24
life in osteoporosis patients specifically regarding physical function and social activities
(Koevska et al., 2019). Physical exercise has a positive effect on muscle tone, balance
and agility; which facilitate Mobility and Usual Activities, which include social activities.
Bone strength can be enhanced through physical exercise, although it is not always visible
by DXA-measurement of the bone (Polidoulis et al., 2012). Exercise did not significantly
improve Pain/Discomfort in the present study. A possible reason for that could be that
Pain/Discomfort may have been present throughout the study. This will be further
discussed in the Discussion of Methods.
All of the osteoporosis patients in the exercise program had been affected by one or
multiple vertebral fractures (Marini et al., 2019). As already mentioned and according to
several studies, these have an exceptionally negative impact on quality of life (Gold,
1996; Begerow et al., 1999; Silverman et al., 2001; Lips & van Schoor, 2005; Borgström
et al., 2005; Jung et al., 2017; Gibbs et al., 2019; Gold et al., 2019; Koevska et al., 2019).
Swedish researchers found that after two years, a hip fracture affected some markers
linked to quality of life, whereas a vertebral fracture affected quality of life in all areas
(Hallberg et al., 2004). In the present study, comorbidities were present in over 90% of
the patients (Marini et al., 2019). A hypothesis is that these consequences for quality of
life and physical function may explain the results of low quality of life among the
osteoporosis patients (Table 1) and the non-significant effect on quality of life through
physical exercise, even though a slightly positive trend was visible (Table 2). Morbidity
of vertebral fractures must be considered by those who design an exercise program.
Marini et al. (2019) provided a safe program for the patients. However, there could be
confounding effects; the present study used a generic questionnaire, which could have led
to difficulty in assessing osteoporosis-specific factors within each marker, since theses
factors could have been overlooked. Taking into account that the exercise had to be
relatively mild to avoid injuries and the limited time given; twice a week for six months,
the exercise program was perhaps not long enough to see clear results, particularly for
Pain/Discomfort or Anxiety/Depression, which were significantly affected by
osteoporosis (Table 1). The effects on quality of life may have been too subtle to be
detected within six months. Also, patients with vertebral fractures have general
difficulties to exercise, according to Silverman (1992). In other words, vertebral fractures
may have such a negative impact on all markers that it may be difficult to obtain
significant results. Nevertheless, there were slightly positive effects of physical exercise,
which may in part have been due to the safety precautions taken.
25
Studies have so far gathered little evidence for physical exercise being beneficial to
patients with vertebral fractures (Gibbs et al., 2019). A therapeutic exercise review of
nine studies showed improvement in strength and balance, but results for pain and quality
of life were inconsistent (Dusdal et al., 2011). During the past ten years, systematic
reviews of physical exercise have confirmed certain benefits in specific markers such as
pain, but not consistently evident results for the overall improvement of quality of life.
The conclusion was that more evidence is required (Gibbs et al., 2019). The effects of
physical exercise after a vertebral fracture were only analyzed in seven trials, according
to Giangregorio et al. (2013) i.e. the first edition of the review by Gibbs et al. (2019). The
studies above had limitations, such as lack of long-term follow-up, bias and small sample
sizes (ibid). Similarly, the present study of postmenopausal women with osteoporosis had
similar drawbacks. To be able to prescribe exercise for patients with vertebral fractures,
a review study by Giangregorio et al. (2013) concluded that a randomized trial of high
quality is required. The Too Fit to Fracture expert panel, including clicicians and
researchers from Australia, Canada, Finland and the U.S., recommended safe exercise
and professional consultation for osteoporosis patients with vertebral fractures, since
negative effects may outweigh the positive for those with multiple fractures, pain, etc.,
such as in the present study (Giangregorio et al., 2014; Marini et al. 2019).
Margaret Martin, Physical Therapist, referred to an exercise trial by Sinaki and
Mikkelsen (1984) that investigated suitable exercises for the spine (vertebrae) among a
group of postmenopausal women. Some of these women complained about back pain and
were examined by DXA. The screenings showed that a larger proportion of those who
performed flexion exercises had fractures (89%) compared to those who performed
extension exercises (16%). This shows that caution needs to be taken for patients with
vertebral fractures. According to Martin, physical trainers may ordinate exercise for
spine-problems that is good for the average population but not for persons with
osteoporosis or low bone mass (Martin, M., 2014). It is important to select a physical
exercise program, which is safe and adapted to osteoporosis patients to prevent vertebral
fractures and improve their physical performance and quality of life.
Osteoporosis affects both the relationship with friends and family; thus, social support is
crucial. Health care systems need to pay attention, not only to bone fragility but to
psychological, social and environmental factors, which are all associated with quality of
life (Gold, 1996). As mentioned in the Introduction, the health values in EQ-5D-3L are
country-specific. Therefore, Jung et al. (2017) have obtained results based on the Korean
26
population norm, while the present study used the Italian one. The present study evaluated
how osteoporosis interferes with the markers linked to the quality of life by using
previously unevaluated data and identified a possible of trend in some of these markers
regarding the positive effect of physical exercise, with almost half a unit (i.e. from 1.5 to
1.0). However, the results were not statistically significant.
6.2 Discussion of Methods
In order to evaluate the methods and possible flaws, it was necessary to find comparable
studies, i.e. those with an exercise program, similar inclusion criteria and study design.
Exercise studies for osteoporosis patients are rare (Marini et al., 2019). The present study
was mainly compared to a quality of life study, by Jung et al. (2017), and a similar
physical exercise study involving osteoporotic women, by Koevska et al. (2019).
These two studies applied two different questionnaires: EQ-5D and QUALEFFO-41,
respectively. The pilot study by Marini et al. (2019) and the present thesis utilized the
EQ-5D-3L. The EQ-5D was assumed to be an appropriate instrument for the present study
as it is associated with the assessment of quality of life, related to osteoporotic spinal
dysfunctions and back pain (Jung et al 2017). As mentioned earlier, the QUALEFFO-41
is specific for measuring quality of life in patients with vertebral fractures, while the EQ-
5D is a generic quality-of-life questionnaire. Because the more detailed questionnaire of
QUALEFFO-41 includes 41 questions instead of 5, as is the case for the EQ-5D-3L
questionnaire, difficulties arose in comparing the results of the current study with those
of the exercise study by Koevska et al. (2019). The EQ-5D-5L, a newer version of the
questionnaire, was used by Jung et al. (2017). The EQ-5D-3L is supposed to cover a
category of problems within only five markers and provides only three answer options.
Patients may therefore find it confusing, or simply tick boxes only because they are
supposed to. This may also be a source of error for the results obtained in the EQ VAS.
According to Kerr et al. (2017), clinical trials seldom estimate patient-reported outcomes,
and in case they do, they only include a small number of markers. This results in difficulty
in observing significant changes resulting from the treatment.
The short time-span was another possible limitation, aside from the shortcomings of the
questionnaire. The exercise program lasted for six months, which Jung et al. (2017)
27
referred to as the required time for a vertebral fracture to heal. Even so, severe pain would
have been present for up to one year after a fracture had healed. According to Huang et
al. (1996), back pain may last for up to four years after a vertebral fracture. The time since
a fracture occurred seemed to affect quality of life more than the number of fractures, as
interpreted by Begerow et al. (1999), who found that the pain started to decrease within
two years. The longer duration of the exercise program in the study by Koevska et al.
(2019) may have produced a clearer effect of physical exercise than the exercise study in
the present thesis. It had more participants (92) who also exercised three times a week,
instead of twice a week, as in the present study. Unfortunately, the time period that had
elapsed since the last fracture of the patients in this study was not recorded (Marini, pers.
comm). The short duration of the intervention may be a reason why physical exercise did
not significantly improve the overall quality of life, nor influence the specific markers:
Pain/Discomfort, Anxiety/Depression and Self-care in the present study.
A possible selection bias could also have occurred, since participation in the exercise
program was non-randomized. The two groups were supposed to be randomized, but all
patients did not want to join the Exercise Group (Marini et al., 2019). The participants in
the Exercise Group generally experienced lower health and physical fitness at the
beginning of the program, which could have led to an emphasis on adjustments to meet
the ability of each patient. Due to the risk of injuries, the study focused on feasibility and
safety with weight-free strengthening exercises, which could have led to a limited
physical challenge. There were no injuries during the study, so the program was safe. The
results obtained with the EQ-5D questionnaire did not detect any influence of the exercise
program on perceived quality of life.
The design of the study by Koevska et al. (2019) was randomized and single-blinded,
thus, it had a superior design in preventing manipulation or bias. It consisted of three
groups instead of two, including a group that combined physical exercise with modalities
of magnetic- and interferential current therapy (for pain reduction) every weekday for 3
weeks. The participants were younger (mean age was 60) than in the present study. Age
could have affected the quality of life in osteoporosis patients and incidence of vertebral
fractures (ibid; Gold et al., 2019; Felsenberg et al., 2002). The randomized design,
younger participants and a longer exercise program with pain-reducing magnetic-and
interferential therapy; could be reasons why the exercise program by Koevska et al.
(2019) resulted in significant improvement.
28
The low number of participants in the exercise program of the present study could have
been due to difficulties in enrolling osteoporosis patients on a voluntary basis. Few
participants may have resulted in a large standard error, which could have caused the
absence of significant results. Moreover, some change in the markers for quality of life
in osteoporosis patients, through participation in the exercise program, may not have been
possible to detect. For example, self-esteem is a contributing factor to life satisfaction
and a higher quality of life. Physical improvement could have led to feelings of
confidence and self-esteem among these patients (Marini et al., 2019). The study by
Koevska et al. (2019), which applied a detailed questionnaire, did observe improved
social life, which highlighted the involvement of social factors. The social aspect of
exercise is also important to the quality of life (Marini et al., 2019; Kendler et al., 2015).
Moreover, sense of coherence has been proven useful as a tool to improve quality of life
after osteoporotic fractures, as seen in the study by Begerow et al. (1999). Sense of
coherence is defined as an individual’s ability to stay healthy through stress management
and health promotion (Antonovsky, 1987). Therefore, it may contribute to quality of life
through improvement of self-reliability and Self-Care.
Regarding Self-care, there were no significant results in the population study (Table 1),
nor in the exercise study (Table 2 & 3). The Italian women in the present study did not
experience considerable problems with Self-care. Similarly, none of the Australian
women in the study by Gandham et al. (2019) experienced Self-care problems. Just as in
the present study, these community dwelling women were reasonably mobile and lived
in a large metropolitan area. Even though the osteoporosis patients in the present study
had suffered vertebral fractures that were assumed to be painful, they were in fact
ambulating and lived at home (Marini et al., 2019). Feelings of uneasiness caused by pain
does not necessarily render a person incapable of Self-care. Vertebral fractures are not
homogenous, and the levels of pain may vary. The pain is usually most severe during the
first six weeks after a fracture, after which it gradually declines. In other cases, the pain
may initially be mild, and then intensify after 6-16 weeks (Lyritis et al., 1989; Silverman,
1992). Moreover, the Australian women were to have had a maximum of 150 minutes of
self-reported exercise per week prior to the study, in order to be included (Gandham et
al., 2019). Just as in the present study, these women were reasonably mobile. A
conclusion can thus be drawn that the inclusion criteria could have influenced Self-care.
Regarding the exercise study, the Exercise Group tended to have lower initial Mobility
29
as compared to the Control Group. It could also have been a factor as to why the persons
in the Exercise Group opted to participate in the exercise program. By engaging in
physical exercise, they could "catch up" in Mobility. Moreover, a decrease in Mobility
can affect Self-care, so since Mobility improved from exercise, it could also explain why
osteoporosis did not affect Self-care among the exercising women in this study.
6.3 Future Research Despite the short duration, the results of the present study were promising and can be a
starting point to design future research, taking into account the following considerations:
• A longer period is needed for exercise studies to detect changes in the
overall quality of life and markers related to the quality of life. This would include
a long-term randomized exercise trial with a follow-up for at least 12 months, as
suggested by Gibbs et al., (2019).
• The safety of the exercise protocol plays a key role in the main intervention
program for osteoporosis patients. In the present study, the safety aspect was taken
into consideration when designing the exercise program. It showed the importance
of including exercise to maximize strength and vitality of the spine, combined
with balance training to prevent falls.
• The selection of an appropriate questionnaire for assessing quality of life in
osteoporosis patients is important for interpreting the results. Quality of life is
complex and may be defined differently according to the cultural habits or
behavioral patterns within a country.
• Since every patient had vertebral fractures, an osteoporosis-specific
questionnaire might have been more suitable, as mentioned by Lips & van Schoor
(2005). A combination of specific and generic methods for evaluation of quality
of life, through the application of both QUALEFFO-41 and EQ-5D-5L, could be
an option. The answers of a questionnaire have subjective elements. The use of
more than one tool can contribute to a deeper understanding of the analyze of the
studied population.
30
7. Conclusions The overall results obtained in this study confirm that osteoporosis negatively affected
quality of life for postmenopausal women. In particular, osteoporosis negatively affected
the markers Mobility, Usual Activities, Pain/Discomfort and Anxiety/Depression in the
studied population. Moreover, the exercise program seemed to improve some markers
linked to quality of life, even if the results did not reach a statistical significance. On the
basis of this evidence, it is possible to propose that health care systems consider the
impact of osteoporosis on quality of life, since a vertebral fracture, a prevalent result of
the disorder, is devastating to the individual. Evaluation of osteoporosis needs to be
prioritized and supportive networks have to be established. This will contribute to social
and economic sustainability.
31
8. References
Agostini, D., Donati, S. Z., Lucertini, F., Annibalini, G., Gervasi, M., Ferri Marini,
C., Piccoli, G., Stocchi, V., Barbieri, E., & Sestili, P. (2018). Muscle and bone
health in postmenopausal women: Role of protein and vitamin D
supplementation combined with exercise training. Nutrients, 10(8), 1103.
https://doi.org/10.3390/nu10081103
Antonovsky, A. (1987) Unraveling the mystery of health: How people manage stress
and stay well. Jossey-Bass.
Auais, M., Al-Zoubi, F., Matheson, A., Brown, K., Magaziner, J., & French, S. D.
(2019). Understanding the role of social factors in recovery after hip fractures: A
structured scoping review. Health & Social Care in the Community, 27(6),
1375–1387. https://doi.org/10.1111/hsc.12830
Begerow, B., Pfeifer, M., Pospeschill, M., Scholz, M., Schlotthauer, T., Lazarescu,
A., Pollaehne, W., & Minne, H. W. (1999). Time since vertebral fracture: An
important variable concerning quality of life in patients with postmenopausal
osteoporosis. Osteoporosis International, 10(1), 26–33.
https://doi.org/10.1007/s001980050190
Benedetti, M. G., Furlini, G., Zati, A., & Letizia Mauro, G. L. (2018). The effectiveness of
physical exercise on bone density in osteoporotic patients. BioMed Research
International, 2018. https://doi.org/10.1155/2018/4840531
32
Brooks, R., Rabin, R., & de Charro, F. (Eds.). (2003). The measurement and
valuation of health status using EQ-5D: A European perspective. Dordrecht:
Springer
Brooks, R., Boye, K. S., & Slaap, B. (2020). EQ-5D: A plea for accurate
nomenclature. Journal of Patient-Reported Outcomes, 4, 52.
https://doi.org/10.1186/s41687-020-00222-9
Borgström, F., Zethraeus, N., Johnell, O., Lidgren, L., Ponzer, S., Svensson, O.,
Abdon, P., Ornstein, E., Lunsjö, K., Thorngren, K. G., Sernbo, I., Rehnberg, C.,
& Jönsson, B. (2006). Costs and quality of life associated with osteoporosis-
related fractures in Sweden. Osteoporosis International, 17(5), 637–650.
https://doi.org/10.1007/s00198-005-0015-8
Choi, M., Prieto-Merino, D., Dale, C., Nüesch, E., Amuzu, A., Bowling, A.,
Ebrahim, S., & Casas, J. P. (2013). Effect of changes in moderate or vigorous
physical activity on changes in health-related quality of life of elderly British
women over seven years. Quality of Life Research, 22(8), 2011–2020.
https://doi.org/10.1007/s11136-012-0332-2
Cauley, J. A., Thompson, D. E., Ensrud, K. C., Scott, J. C., & Black, D. (2000). Risk of
mortality following clinical fractures. Osteoporosis International, 11(7), 556–561.
https://doi.org/10.1007/s001980070075
33
Cipriani, C., Pepe, J., Bertoldo, F., Bianchi, G., Cantatore, F. P., Corrado, A., Di
Stefano, M., Frediani, B., Gatti, D., Giustina, A., Porcelli, T., Isaia, G., Rossini,
M., Nieddu, L., Minisola, S., Girasole, G., & Pedrazzoni, M. (2018). The
epidemiology of osteoporosis in Italian postmenopausal women according to the
National Bone Health Alliance (NBHA) diagnostic criteria: A multicenter cohort
study. Journal of Endocrinological Investigation, 41(4), 431–438.
https://doi.org/10.1007/s40618-017-0761-4
Cosman, F., de Beur, S. J., LeBoff, M. S., Lewiecki, E. M., Tanner, B., Randall, S.,
Lindsay, R., & National Osteoporosis Foundation. (2014). Clinician's guide to
prevention and treatment of osteoporosis. Osteoporosis International, 25(10),
2359–2381. https://doi.org/10.1007/s00198-014-2794-2
Cranney, A., Jamal, S. A., Tsang, J. F., Josse, R. G., & Leslie, W. D. (2007).
Low bone mineral density and fracture burden in postmenopausal women.
Canadian Medical Association Journal, 177(6), 575–580.
https://doi.org/10.1503/cmaj.070234
Cummings, S. R., Black, D. M., Nevitt, M. C., Browner, W., Cauley, J., Ensrud, K.,
Genant, H. K., Palermo, L., Scott, J., & Vogt, T. M. (1993). Bone density at
various sites for prediction of hip fractures. The Lancet (London, England),
341(8837), 72–75. https://doi.org/10.1016/0140-6736(93)92555-8
dos Santos Silva et al. (2019). Evaluation of a program of physical exercise on
blood markers and sleep quality in elderly. Revista Andaluza de Medicina del
Deporte, 12(4), 363-367. https://doi.org/10.33155/j.ramd.2019.05.009
34
Dusdal, K., Grundmanis, J., Luttin, K., Ritchie, P., Rompre, C., Sidhu, R., &
Harris, S. R. (2011). Effects of therapeutic exercise for persons with
osteoporotic vertebral fractures: A systematic review. Osteoporosis
International, 22(3), 755–769. https://doi.org/10.1007/s00198-010-1497-6
EuroQol Research Foundation. (2020). Terminology. EQ-5D.
https://euroqol.org/support/terminology
EuroQol Research Foundation. (2018). EQ-5D-3L User Guide: Basic Information on how
to use the EQ-5D-3L Instrument (Version 6.0). EQ-5D.
https://euroqol.org/publications/user-guides
Fechtenbaum, J., Cropet, C., Kolta, S., Horlait, S., Orcel, P., & Roux, C. (2005).
The severity of vertebral fractures and health-related quality of life in
osteoporotic postmenopausal women. Osteoporosis International, 16(12), 2175–
2179. https://doi.org/10.1007/s00198-005-2023-0
Felsenberg et al. (2002). Incidence of vertebral fracture in Europe: Results from the
European Prospective Osteoporosis Study (EPOS). Journal of Bone and Mineral
Research, 17(4), 716–724. https://doi.org/10.1359/jbmr.2002.17.4.716
Gandham, A., McMillan, L. B., Ng, C. A., Humbert, L., Bonham, M. P., Zengin,
A., Ebeling, P. R., & Scott, D. (2019). Associations of health-related quality of
life, fear of falling and objective measures of physical function with bone health
35
in postmenopausal women with low bone mass. Journal of Clinical Medicine,
8(9),13. https://doi.org/10.3390/jcm8091370
Giangregorio, L. M., MacIntyre, N. J., Thabane, L., Skidmore, C. J., &
Papaioannou, A. (2013). Exercise for improving outcomes after osteoporotic
vertebral fracture. The Cochrane Database of Systematic Reviews, (1).
https://doi.org/10.1002/14651858.CD008618.pub2
Giangregorio, L. M., Papaioannou, A., MacIntyre, N. J., Ashe, M. C., Heinonen,
A., Shipp, K., Wark, J., McGill, S., Keller, H., Jain, R., Laprade, J., & Cheung,
A. M. (2014). Too Fit to Fracture: Exercise recommendations for individuals
with osteoporosis or osteoporotic vertebral fracture. Osteoporosis International,
25(3), 821–835. https://doi.org/10.1007/s00198-013-2523-2
Gibbs, J. C., MacIntyre, N. J., Ponzano, M., Templeton, J. A., Thabane, L.,
Papaioannou, A., & Giangregorio, L. M. (2019). Exercise for improving
outcomes after osteoporotic vertebral fracture. Cochrane Database of Systematic
Reviews, (7). https://doi.org/10.1002/14651858.CD008618.pub3
Gold D. T. (1996). The clinical impact of vertebral fractures: Quality of life in
women with osteoporosis. Bone, 18(3), 185–189. https://doi.org/10.1016/8756-
3282(95)00500-5
Gold, D. T., Williams, S. A., Weiss, R. J., Wang, Y., Watkins, C., Carroll, J.,
Middleton, C., & Silverman, S. (2019). Impact of fractures on quality of life in
36
patients with osteoporosis: A US cross-sectional survey. Journal of Drug
Assessment, 8(1), 175–183. https://doi.org/10.1080/21556660.2019.1677674
Haczynski, J., & Jakimiuk, A. J. (2001). Vertebral fractures: A hidden problem of
osteoporosis. Medical Science Monitor, 7(5), 1108–1117.
Hallberg, I., Rosenqvist, A. M., Kartous, L., Löfman, O., Wahlström, O., & Toss,
G. (2004). Health-related quality of life after osteoporotic fractures.
Osteoporosis International, 15(10), 834–841. https://doi.org/10.1007/s00198-004-
1622-5
Hernlund, E., Svedbom, A., Ivergård, M., Compston, J., Cooper, C., Stenmark, J.,
McCloskey, E. V., Jönsson, B., & Kanis, J. A. (2013). Osteoporosis in the
European Union: Medical management, epidemiology and economic burden.
Archives of Osteoporosis, 8(1-2), 136. https://doi.org/10.1007/s11657-013-0136-
1
Huang, C., Ross, P. D., & Wasnich, R. D. (1996). Vertebral fractures and other
predictors of back pain among older women. Journal of Bone and Mineral
Research, 11(7), 1026–1032. https://doi.org/10.1002/jbmr.5650110721
IBM Corporation. (2016). IBM SPSS Statistics for Windows (Version 24.0) [Computer
software]
Jung, H. J., Park, Y. S., Seo, H. Y., Lee, J. C., An, K. C., Kim, J. H., Shin, B. J.,
Kang, T. W., & Park, S. Y. (2017). Quality of life in patients with osteoporotic
37
vertebral compression fractures. Journal of Bone Metabolism, 24(3), 187–196.
https://doi.org/10.11005/jbm.2017.24.3.187
Kannus, P., Haapasalo, H., Sankelo, M., Sievänen, H., Pasanen, M., Heinonen, A.,
Oja, P., & Vuori, I. (1995). Effect of starting age of physical activity on bone
mass in the dominant arm of tennis and squash players. Annals of Internal
Medicine, 123(1), 27–31. https://doi.org/10.7326/0003-4819-123-1-199507010-
00003
Kannus P. (1999). Preventing osteoporosis, falls, and fractures among elderly
people. Promotion of lifelong physical activity is essential. British Medical
Journal (Clinical Research Edition), 318(7178), 205–206.
https://doi.org/10.1136/bmj.318.7178.205
Kanis, J. A., Johnell, O., Oden, A., Borgstrom, F., Zethraeus, N., De Laet, C., &
Jonsson, B. (2004). The risk and burden of vertebral fractures in Sweden.
Osteoporosis International, 15(1), 20–26. https://doi.org/10.1007/s00198-003-
1463-7
Kendler, D. L., Bauer, D. C., Davison, K. S., Dian, L., Hanley, D. A., Harris, S. T.,
McClung, M. R., Miller, P. D., Schousboe, J. T., Yuen, C. K., & Lewiecki, E.
M. (2016). Vertebral fractures: Clinical importance and management. The
American Journal of Medicine, 129(2).
https://doi.org/10.1016/j.amjmed.2015.09.020
38
Kerr, C., Bottomley, C., Shingler, S., Giangregorio, L., de Freitas, H. M., Patel, C.,
Randall, S., & Gold, D. T. (2017). The importance of physical function to
people with osteoporosis. Osteoporosis International, 28(5), 1597–1607.
https://doi.org/10.1007/s00198-017-3911-9
Koevska, V., Nikolikj-Dimitrova, E., Mitrevska, B., Gjeracaroska-Savevska, C.,
Gocevska, M., & Kalcovska, B. (2019). Effect of exercises on quality of life in
patients with postmenopausal osteoporosis—Randomized trial. Open Access
Macedonian Journal of Medical Sciences, 7(7), 1160–1165.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490505/
Krølner, B., Toft, B., Pors Nielsen, S., & Tøndevold, E. (1983). Physical exercise
as prophylaxis against involutional vertebral bone loss: A controlled trial
[Abstract]. Clinical Science 64(5), 541–546. https://doi.org/10.1042/cs0640541
Lentle, B. C., Brown, J. P., Khan, A., Leslie, W. D., Levesque, J., Lyons, D. J.,
Siminoski, K., Tarulli, G., Josse, R. G., Hodsman, A., Scientific Advisory
Council of Osteoporosis Canada, & Canadian Association of Radiologists
(2007). Recognizing and reporting vertebral fractures: reducing the risk of future
osteoporotic fractures. The Canadian Association of Radiologists Journal, 58(1),
27–36. https://pubmed.ncbi.nlm.nih.gov/17408160/
Lerner, U. H., Kindstedt, E., & Lundberg, P. (2019). The critical interplay between
bone resorbing and bone forming cells. Journal of Clinical Periodontology,
46(Suppl. 21), 33–51. https://doi.org/10.1111/jcpe.13051
39
Lips, P., & van Schoor, N. M. (2005). Quality of life in patients with osteoporosis.
Osteoporosis International, 16(5), 447–455. https://doi.org/10.1007/s00198-
004-1762-7
Lydick, E., Zimmerman, S. I., Yawn, B., Love, B., Kleerekoper, M., Ross, P.,
Martin, A., & Holmes, R. (1997). Development and validation of a
discriminative quality of life questionnaire for osteoporosis (the OPTQoL).
Journal of Bone and Mineral Research, 12(3), 456–463.
https://doi.org/10.1359/jbmr.1997.12.3.456
Lyritis, G. P., Mayasis, B., Tsakalakos, N., Lambropoulos, A., Gazi, S.,
Karachalios, T., Tsekoura, M., & Yiatzides, A. (1989). The natural history of the
osteoporotic vertebral fracture. Clinical Rheumatology, 8(Suppl. 2), 66–69.
https://doi.org/10.1007/BF02207237
Madureira, M. M., Ciconelli, R. M., & Pereira, R. M. (2012). Quality of life
measurements in patients with osteoporosis and fractures. Clinics, 67(11), 1315–
1320. https://doi.org/10.6061/clinics/2012(11)16
Marini, S., Leoni, E., Raggi, A., Sanna, T., Malavolta, N., Angela, B., Maietta
Latessa, P., & Dallolio, L. (2019). Proposal of an adapted physical activity
exercise protocol for women with osteoporosis-related vertebral fractures: A
pilot study to evaluate feasibility, safety, and effectiveness. International
Journal of Environmental Research and Public Health, 16(14), 2562.
https://doi.org/10.3390/ijerph16142562
40
Marshall, D., Johnell, O., & Wedel, H. (1996). Meta-analysis of how well measures
of bone mineral density predict occurrence of osteoporotic fractures. British
Medical Journal (Clinical Research Edition), 312(7041), 1254–1259.
https://doi.org/10.1136/bmj.312.7041.1254
Martin, M. (2014, December 23). Osteoporotic vertebral compression fractures
[Video]. YouTube. https://www.youtube.com/watch?v=UYze5MB4qYo
McCloskey, E. V., Harvey, N. C., Johansson, H., Lorentzon, M., Vandenput, L.,
Liu, E., & Kanis, J. A. (2020). Global impact of COVID-19 on non-
communicable disease management: Descriptive analysis of access to FRAX
fracture risk online tool for prevention of osteoporotic fractures. Osteoporosis
International. 32(1), 39–46. https://doi.org/10.1007/s00198-020-05542-6
National Health Service. (2019, June 18). Overview: Osteoporosis. Retrieved
November 8, 2020, from https://www.nhs.uk/conditions/osteoporosis/
National Institute of Arthritis and Musculoskeletal and Skin Diseases. (n.d.).
Osteoporosis overview. National Institutes of Health Osteoporosis and Related
Bone Diseases National Resource Center. https://www.bones.nih.gov/health-
info/bone/osteoporosis/overview
National Osteoporosis Foundation. (2020, December 21). What women need to know.
Retrieved February 12, 2021 from, https://www.nof.org/preventing-fractures/general-
facts/what-women-need-to-know/
41
Owen, N., Healy, G. N., Dempsey, P. C., Salmon, J., Timperio, A., Clark, B. K.,
Goode, A. D., Koorts, H., Ridgers, N. D., Hadgraft, N. T., Lambert, G., Eakin,
E. G., Kingwell, B. A., & Dunstan, D. W. (2020). Sedentary behavior and public
health: Integrating the evidence and identifying potential solutions. Annual
Review of Public Health, 41, 265–287. https://doi.org/10.1146/annurev-
publhealth-040119-094201
Patrick, D. L., Starks, H. E., Cain, K. C., Uhlmann, R. F., & Pearlman, R. A.
(1994). Measuring preferences for health states worse than death. Medical
Decision Making, 14(1), 9–18. https://doi.org/10.1177/0272989X9401400102
Polidoulis, I., Beyene, J., & Cheung, A. M. (2012). The effect of exercise on pQCT
parameters of bone structure and strength in postmenopausal women—
A systematic review and meta-analysis of randomized controlled trials.
Osteoporosis International 23(1), 39–51. https://doi.org/10.1007/s00198-011-
1734-7
Rabin, R., & de Charro, F. (2001). EQ-5D: A measure of health status from the
EuroQol Group. Annals of Medicine, 33(5), 337–343.
https://doi.org/10.3109/07853890109002087
Reginster, J. Y., & Burlet, N. (2006). Osteoporosis: a still increasing prevalence.
Bone, 38(2, Suppl. 1), 4–9. https://doi.org/10.1016/j.bone.2005.11.024
Recknor, C. P., Grant, S. L., Recknor, J. C., & MacIntyre, N. J. (2013). Scores on
the safe functional motion test are associated with prevalent fractures and fall
42
history. Physiotherapy Canada, 65(1), 75–83. https://doi.org/10.3138/ptc.2011-
25BH
Salminen, H., Piispanen, P., & Toth-Pal, E. (2019). Primary care physicians' views
on osteoporosis management: A qualitative study. Archives of Osteoporosis,
14(1), 48. https://doi.org/10.1007/s11657-019-0599-9
Silverman S. L. (1992). The clinical consequences of vertebral compression
fracture. Bone, 13(Suppl. 2), S27–S31. https://doi.org/10.1016/8756-
3282(92)90193-z
Silverman, S., Minshall, M., Shen, W., Harper, K. and Xie, S. (2001). The
relationship of health-related quality of life to prevalent and incident vertebral
fractures in postmenopausal women with osteoporosis: Results from the multiple
outcomes of Raloxifene evaluation study. Arthritis & Rheumatism, 44(11),
2611-2619. https://doi.org/10.1002/1529-0131(200111)44:11<2611::aid-
art441>3.0.co;2-n
Sinaki, M., & Mikkelsen, B. A. (1984). Postmenopausal spinal osteoporosis:
Flexion versus extension exercises. Archives of Physical Medicine and
Rehabilitation, 65(10), 593–596. Retrieved from
https://pubmed.ncbi.nlm.nih.gov/6487063/m
Sinaki, M. (2012). Exercise for patients with osteoporosis: Management of
vertebral compression fractures and trunk strengthening for fall prevention. PM
43
& R: The Journal of Injury, Function, and Rehabilitation, 4(11), 882–888.
https://doi.org/10.1016/j.pmrj.2012.10.008
Sinaki, M. (2013). Yoga spinal flexion positions and vertebral compression fracture
in osteopenia or osteoporosis of spine: Case series. Pain Practice, 13(1), 68–75.
https://doi.org/10.1111/j.1533-2500.2012.00545.x
Singer, A., Exuzides, A., Spangler, L., O'Malley, C., Colby, C., Johnston, K.,
Agodoa, I., Baker, J., & Kagan, R. (2015). Burden of illness for osteoporotic
fractures compared with other serious diseases among postmenopausal women
in the United States. Mayo Clinic Proceedings, 90(1), 53–62.
https://doi.org/10.1016/j.mayocp.2014.09.011
Smith, R. (1985). Exercise and osteoporosis. British Medical Journal, 290(6476),
1163–1164. https://doi.org/10.1136/bmj.290.6476.1163
Stanghelle, B., Bentzen, H., Giangregorio, L., Pripp, A. H., & Bergland, A. (2019).
Associations between health-related quality of life, physical function and pain in
older women with osteoporosis and vertebral fracture. BMC Geriatrics, 19(1),
298. https://doi.org/10.1186/s12877-019-1268-y
Suzuki, N., Ogikubo, O., & Hansson, T. (2010). Previous vertebral compression
fractures add to the deterioration of the disability and quality of life after an
acute compression fracture. European Spine Journal, 19(4), 567–574.
https://doi.org/10.1007/s00586-009-1162-y
44
Swedish Research Council. (2017). Good research practice. 354-357.
https://www.vr.se/english/analysis/reports/our-reports/2017-08-31-good-
research-practice.html
Szende, A., Janssen, B. & Cabases, J. (2014). Self-reported population health: An
international perspective based on EQ-5D. 1st ed. Dordrecht: Springer. 101-105
Tella, S. H., & Gallagher, J. C. (2014). Prevention and treatment of postmenopausal
osteoporosis. The Journal of Steroid Biochemistry and Molecular Biology, 142,
155–170. https://doi.org/10.1016/j.jsbmb.2013.09.008
Testa, M. A., & Simonson, D. C. (1996). Assessment of quality-of-life outcomes. The
New England Journal of Medicine, 334(13), 835–840.
https://doi.org/10.1056/NEJM199603283341306
United Nations, Department of Economic and Social Affairs, Population
Division. (2011). World population prospects: The 2010 revision, Volume I:
Comprehensive Tables (ST/ESA/SER.A/313).
https://www.un.org/en/development/desa/population/publications/pdf/trends/WP
P2010/WPP2010_Volume-I_Comprehensive-Tables.pdf
United Nations General Assembly. (2015, October 15). Transforming our world:
The 2030 agenda for sustainable development (A/RES/70/1).
https://www.un.org/en/development/desa/population/migration/generalassembly
/docs/globalcompact/A_RES_70_1_E.pdf
45
van Schoor, N. M., Knol, D. L., Glas, C. A., Ostelo, R. W., Leplège, A., Cooper,
C., Johnell, O., & Lips, P. (2006). Development of the Qualeffo-31, an
osteoporosis-specific quality-of-life questionnaire. Osteoporosis International,
17(4), 543–551. https://doi.org/10.1007/s00198-005-0024-7
Whedon, G. D. (1984). Disuse osteoporosis: Physiological aspects. Calcified Tissue
International, 36(Suppl. 1), S146–S150. https://doi.org/10.1007/BF02406148
World Health Organization. (2011). Non-communicable diseases country profiles 2011.
https://www.who.int/nmh/publications/ncd_profiles2011/en/