Richard S. Pope MPAS, PA-C DFAAPAArthritis Center of CT

Waterbury, CTDanbury Orthopedics

Danbury, CT

OSTEOPOROSIS CASE STUDIESWhere to use what FDA approved

Medicine and When.

Faculty Disclosures

• Amgen- Advisory committee denosumab• URL Pharma-Advisory committee and

speaker’s bureau colchicine• UCB Pharma-Speaker’s Bureau certolizumab

• Takeda-Speaker’s bureau febuxostat

By using case studies at the end of this session the participant will be able to choose treatment or not based on the scenarios listed below:

1. Perimenopausal osteopenia with a family history of osteoporosis (To treat or not to treat?)

2. Osteoporosis by BMD without fracture in a sixty five year old female

3. Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD)

4. Severe osteoporosis with a T-score of <-3.0 with fractures (Case for anabolic treatment)

5. Osteoporosis in a PMP female with CKD stage 4(15-29 ml/min/1.73²)

Case 1Perimenopausal osteopenia with a family history of osteoporosis

(To treat or not to treat?)

• 56 year old W/F routine GYN appt. and follow up of stage II b breast CA.

• Rxed with surgery Xs 2 for lumpectomy at age 44• Six weeks of localized radiation to right breast• Chemotherapy 6 rounds of epirubicin, cytoxan and 5FU,

adjuvant therapy of aromatase inhibition Xs 2 yrs.Tamoxifen for first three years.

• No menses after chemotherapy age 44BMD T-score of -2.1 in femoral neck No fractures as an adult.Mother treated for OP at age 88 GM fractured hip

Case 1Perimenopausal osteopenia with a family history of osteoporosis

(To treat or not to treat?)

• Secondary work up for OP included:– CBC, comp. chem profile, 24 hr. urine ca+, celiac

panel, Vit. D 25 OH D level, protein electrophoresisResults

– + for Vit. D of 13ng/ml– 5’ 5’’ 147 lbs. FRAX?

Secondary osteoporosisFRAX calculator

• Enter yes if the patient has a disorder strongly associated with osteoporosis. These include type I (insulin dependent) diabetes, osteogenesis imperfecta in adults, untreated long-standing hyperthyroidism, hypogonadism or premature menopause (<45 years), chronic malnutrition, or malabsorption and chronic liver disease

Case 1Perimenopausal osteopenia with a family history of osteoporosis

(To treat or not to treat?)

How would you manage this patient?1. Because of her + family history and low Vit D

level would go ahead and treat with FDA

approved meds.2. Replete patient with high doses of Vit D3. Recommend weight bearing exercises, Ca+

1200mg/day and vitamin D 800 IU/day4. Re-check the Vit D level in three months after

replacement.

Case 2Osteoporosis by BMD without fracture in a sixty five year old female

• 65 year old comes for routine physical and you note that she has not had a prior BMD DXA

PMHx: GERD, Barrett’s esophagusHypertensionOP risk factores: no hx of fx as an adultNo parental history of hip fracture but mother had multiple compression fractures and associated height lossShe smokes about 15 cigarettes/day and unable to give up the habitDrinks 2+ glasses of wine daily

Case 2Osteoporosis by BMD without fracture in a sixty five

year old female

• MEDs:-losartan 50mg-esomeprazole 40mg Barrett’s esophagus-Ibuprofen 400 prn HA and joint pain-MVI (200iu Vit D2 ergocalciferol)-Calcium carbonate 1,000mg-Vit D3(cholecalciferol 1,000 IU daily)

Case 2Osteoporosis by BMD without fracture in a sixty five

year old female

• Lab work up shows Vit D 21ng/ml otherwise negative

• BMD T-score in the lumbar spine is -2.5To treat or not to treat?

1. Pt is at risk for esophageal side effects 2nd to GERD

2. Barrett’s esophagus As a result would avoid oral bisphosphonates

Case 2Osteoporosis by BMD without fracture in a sixty five

year old female

• Management optionsPt preference (discuss pros and cons)Raloxifene STAR trial, RUTH trialIV bisphosphonates:

-zoledronic acid (data in spine/hip/non-vertebral)-ibandronate(data for spine not hip)

CASE 3Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD)

Sally, age 65, has been concerned over her bone health as a result of fracturing her wrist last month. She is referred to you as her PCP for evaluation by her orthopedist. She twisted her foot and fell on an outstretched hand and sustained a Colles fracture.

History:1. No parental history of fracture2. She did smoke but has not since she was 453. She drinks 1-2 glasses of wine every night. Denies alcohol abuse4. She gets plenty of sunlight and was just in FL with her 3 grown

daughters.5. Other than her wrist fracture no other fractures as an adult.

CASE 3Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD)

• PE: height 5’6” stadiometer 1.5 inch loss• Weight 176 lbs• Very mild kyphosis• Gait and stability tests good.• Gets up without arm rests

Case 3What would you do next to work up this patient?

CHOOSE AS MANY AS ARE CORRECT

1. BMD2. Chemistry profile, CBC, Vit D 25 level etc.3. Dorsal spine x-ray4. Use FRAX™ Calculator

CASE 3Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD)

• DXA BMD femoral neck T-score -2.2• Laboratory work-up Vit D 28ng/ml• 24 hour urine calcium <200mg/dcl (nml)• iPTH and ionized Calcium (wnl)• Celiac panel negative• SPEP normal• D-spine x-ray negative for morphometric

fracture

Case 4 Severe osteoporosis with a T-score of <-3.0 with fractures (Case for anabolic treatment)

• 79 year old male• Asymptomatic compression Fxs T-10 and L-4• Parkinson’s Disease• Recent wrist fracture• T-Scores:

– Spine -3.0 T score at L-S 2-4– Hip -2.8

• Severe osteoporosis (osteoporotic fx and BMD -2.5 or worse)

Case 4 Severe osteoporosis with a T-score of <-3.0 with fractures (Case for anabolic

treatment)

Treatment considerations

• 12 fold increased risk for subsequent vertebral fxs.• Is at extremely high risk for falls 2° Parkinson’s• Needs fall protection, home inspection for loose

rugs and well lit bathrooms especially at night.• Needs aggressive therapy for severe osteoporosis.

• Increased spinal BMD 9%

• 96% of women showed an increase in BMD• Increased femoral neck BMD 3% • Reduced new/worsening back pain • Reduced fracture-associated height loss

• Reduced risk of new vertebral fractures by 65%• Reduced risk of moderate and severe vertebral fractures by

90%• Reduced risk of non-vertebral fragility fractures by 53%• Studies are too small to evaluate effect on hip fracture

TeriparatiderhPTH [1-34]

20 mcg SQ qD

Neer et al. N Engl J Med 2001; 344:1434-41

Case 5Osteoporosis in a patient CKD stage 4

• 86 year old female s/p CVA uses cane and has a dense left hemiparesis

• Her BMD show a -3.1 BMD in her left hip• She has a history of borderline renal function

and has an eGFR of 33ml/min.• She is hypertensive, diabetic and on lisinopril,

insulin glargine, pravastatin, baby ASA and coumadin.

Case 5Osteoporosis in a patient with renal disease

Labs:• Vit D 36ng/ml• iPTH and ionized Ca+ wnl• 24 hour urine Calcium wnl• SPEP and Celiac panel are normal • Cockcroft-Gault method GFR 33mls/minute

Bisphosphonates are renally cleared and are contraindicated below 35ml/minute GFR

www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation

Case 5Osteoporosis in a patient with renal disease

Treatment Recommendations

• Denosumab—is not renally excreted and therefore no dosage adjustments are required for patients with chronic kidney disease. (creatinine clearance <30 mL/min).

• Patients in this population are more likely to have hypocalcemia and this is a contraindication to its use.

• Screening labs should be performed for ca+ level. Phosphorus and mg+ and repeat calcium in renal pts is recommended ten days after dosing. If serum calcium is low calcium levels should be corrected. If pt does not have renal disease serum ca+ not required.

Denosumab for osteoporosis uptodate version 19.2Accessed 7-11-2011

RANKL Antibody/RANKL: Activation Of Osteoclasts

Activated osteoclast

CFU-M

Pre-fusion osteoclast

Multinucleatedosteoclast

Bone

OB

Growth factors Hormones

Cytokines

RANKOPG RANKL

RANK = Receptor Activator of Nuclear factor Kappa BRANKL = RANK LigandCFU-M = Colony-Forming-Unit MacrophageOPG = Osteoprotegerin

Adapted from Boyle, et al. Nature 2003;423:337

OP

GDenosumab

Y

Y

YY

Y

YY

Slide courtesy of Steve Harris MD

Safe and effective therapies are availableAntiresorptive agents

i Prevent bone loss and preserve architecturei Improve quality of bonei Reduce the risk of vertebral fractures (all agents)i Alendronate, risedronate and zoledronic acid proven to reduce the risk of

nonvertebral and hip fractures

Anabolic agent: rhPTH [1-34] (teriparatide) i Increases bone density and sizei Improves quality of bonei Reduces the risk of vertebral and nonvertebral fractures; no hip fracture

dataRankL inhibitors (denosumab)

• Inhibits function and survival of osteoclasts via RankL inhibition• Prevents bone loss by decreasing bone turnover• Reduces risk of vertebral, non-vertebral and hip fractures• Indicated for treatment of PMP only (July 2011)

Patient factors determine the most appropriate drug to use

Treatment: Summary

1 AWP (Average Wholesale Price) varies by region and distributor* Medi-Span Drug Data. Price Rx® Prescription drug database (Accessed 30 October 2009)

Red Book: Pharmacy’s Fundamental Reference. Thomson Medical Economics: Montvale, NJ. 2007.

Drugs to Treat Osteoporosis

Cost per Effect on Fracture Risk

Agent year1 Vertebral Nonvert

HipRaloxifene $976* -- --

Calcitonin $1,517* -- --

Brand alendronate $1,103 Generic alendronate $108

Risedronate $1,110

Ibandronate (oral) $1,024 -- --Ibandronate (IV) $1,938

Zoledronic acid $1,249 Teriparatide $9,786 --

: antifracture efficacy proven in clinical trial --: antifracture efficacy not proven in clinical trial

Case Summaries

1. Perimenopausal female with a low bone density. FRAX calculator and treat with life style and Vit D and Ca+.2. OP by lumbar T-score and no fx–history of Barrett’s, GERD. Avoid oral bisphosphonates, consider IV bisphosphonates or raloxifene.3. Wrist fracture in a sixty five year old. Fracture trumps the DXA. FDA approved meds.

Case Summaries Continued

4. Severe OP multiple compression fxs, T-score -3.0. Case for anabolic agent.

5. OP in a CKD stage 4- RankL inhibition in renal pts where bisphosphonates are contraindicated

Thank you

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