Protein IntakeProtein is generally considered to have an anabolic effect on bone. A high dietary protein intake over a 2-week period has little or no effect on calcium metabolism or bone turnover in healthy adult women (Kerstetter et al., 2005). On the other hand, a chronic low protein intake contributes to low levels of serum albumin, which lowers both serum IGF-l and serum calcium, a situation in which fracture patients may be especially vulnerable.

These two aspects of protein intake-high versus low- on bone health can be explained by two distinct metabolic actions of proteins and their absorbed amino acids: an anabolic effect on bone and a catabolic effect on bone resulting from the generation of an acid load. In most diets the two effects generally offset each other; but at extremes of intake, either very high or very low, one metabolic action will dominate and affect BMC and BMD (Sebastian, 2005).

A normal adult protein intake of approximately 1 g/kg of body weight maintains the serum PTH concentration within a healthy range (Kerstetter et al., 2000) if calcium intake is also at or near the recommended intake. Chil- dren and adolescents may need a similar protein intake to support optimal skeletal growth (Alexy et al., 2005). IGF -1 production drives the anabolic effect without ex- cessive generation of net acid resulting from the catabo- lism of the amino acids; the difference between the ana- bolic effect and the catabolic action results in bone gain or bone loss (Sebastian, 2005). On the other hand, a low protein intake, such as in undernutrition, generates a decreased serum concentration of IGF-l (Ammann et aI., 2000).

Animal protein increases urinary losses of calcium fol- lowing each meal containing large amounts of animal pro- tein and over lengthy periods of high animal protein con- sumption, whereas a plant-based diet (e.g., one rich in soy protein) has little effect on urinary calcium losses because of the production of a neutral or basic urine (Wengreen et al.,2004) (see Clinical Insight: Acid Ash and Alkaline Ash Dietsin Chapter 36). However, urinary calcium losses have been suggested to be similar for both plant and animal proteins following relatively long-term consumption (Bonjour, 2005). Therefore the relationship between protein and calcium remains unsettled.

Magnesium IntakeMore than 50% of the magnesium in the body is found in bone tissue, but the role of this mineral in bone functions is poorly understood. The largest percentage of the mag- nesium ions in bone exists in the bone fluids, but a smaller fraction of these ions is bound in the bone crystals, prob- ably at the surfaces only. A small percentage of the mag- nesium ions are located within bone cells, where they serve as enzyme cofactors, as in all other cells. Magnesium dietary deficits seem to have little effect on bone tissue, but one report suggests that adequate intakes of magne- sium improve BMD (Ryder et al., 2005).

CHAPTER 24 I Nutrition and Bone Health 625

Vitamin K IntakeVitamin K is an essential micronutrient for bone health. Its role in posttranslational modification of several matrix pro- teins, including osteocalcin, is now well established. Osteo- calcin, a bone-specific protein made by osteoblasts, requires vitamin K for its posttranslational carboxylation (i.e., matu- ration). This molecule is secreted into the bone matrix, where the roles of osteocalcin are not well characterized, except that it appears to be involved in the mineralization process-perhaps acting to stop the formation of crystals to prevent overmineralization. Some osteocalcin is also se- creted by osteoblasts directly into the circulating blood.

A second way that osteocalcin enters blood is followingbone resorption and the release of these molecules; in this way, osteocalcin serves as a serum bone marker for predict- ing the risk of a fracture. Many elderly individuals, perhaps as high as 50%, have inadequate intakes of vitamin K, pri- marily because their consumption of dark-green leafy veg- etables is so low. In one study vitamin K supplementation of postmenopausal women was shown to retard bone loss (Braam et aI., 2003). Therefore an optimal intake of this fat- soluble vitamin, especially later in life, may be important for bone health, the reduction of fractures, and calcium homeo- stasis (Vermeer et al., 2004). It is important to consider the vitamin K intake in older persons who may also be taking blood-thinning medications. Therapeutic INR ranges are achieved with vitamin K in low dose supplementation, and fluctuations are few (Ford et al., 2007) (see Chapter 16).

Vitamin A (Retinol) IntakeVitamin A consumption is generally considered to be ben- eficial to bone growth and maintenance. However, results of recent epidemiologic studies suggest that excessive reti- nal consumption, but not from carotenoids per se, may contribute to hip fractures (Feskanich et al., 2002; Prom- islow et al., 2002; Michaelsson et al., 2003; Wengreen et al., 2004). Two reports did not find an association between vitamin A and increased risk of fractures (Rejnmark et al.,2004; Barker et al., 2005). Nevertheless, concern remainsthat the combined intakes of supplemental vitamin A and vitamin A from fortified foods may be too high in the United States, especially in health-conscious postmeno- pausal white females. The window of safe consumption of vitamin A is fairly narrow, but it may be even narrower for the elderly (Anderson, 2002).

Trace Mineral IntakesRelatively few studies are available about the effects of trace elements on bone. Iron, zinc, copper, manganese, and boron may function in bone cells, but their specific roles in preventing bone loss are not well established. In one study the supplementation of several trace elements (copper, fluoride, manganese, and zinc) along with calcium for 1 year resulted in a reduced loss of lumbar BMD com- pared to the greater loss in a control group receiving only calcium (Nieves, 2005). The skeletal roles of several trace elements are briefly noted.