Osteoporosis

Osteoporosis is a progressive deterioration in bone microarchitecture associated with loss of bone mineral density (BMD), leading to increasing risk of fracture with time. The prevalence of this condition in the United States exceeds 12 million adults 50 years old or older, with more than 40 million additional older adults at higher risk of developing osteoporosis because of low BMD. Black adults tend to have a lower prevalence of osteoporosis and fracture than white adults.

Osteoporotic bone tissue shows deterioration of microarchitecture, with thinner trabeculae, reduced mineralization, and thinning of cortical surfaces associated with increased cortical porosity. Total BMD is the result of a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts during continuous remodeling. During childhood, bone growth requires a balance in favor of bone acquisition and peak bone mass, whereas in young adults, BMD tends to be relatively stable. With aging, osteoclast activity begins to exceed that of osteoblasts and loss of bone occurs. After the onset of menopause in women, bone loss accelerates to two to six times premenopausal rates, and then gradually slows to about 1% annually by 10 years after menopause. Individually, changes in bone mass also reflect numerous

exposures that affect the remodeling balance. Therefore, osteoporosis prevention depends on optimizing peak bone mass, minimizing exposures that lead to bone loss, and optimizing nutritional exposures for bone maintenance throughout life.

Measuring BMD to define osteoporosis is important because an inverse relationship exists with risk of fracture in older adults. Risk of fracture increases with age because of changes in bone quality, declining bone density, and falls, which increase with aging because of declining muscle strength, loss of balance, gait difficulties, arthritis, poor vision, and use of medications.

As living tissue, with constant resorption and rebuilding, bone appears to be responsive to a wide range of nutrients. Some of these have only recently been understood and others continue to be actively investigated.

Calcium is the major mineral component of bone mass, and nearly 99% of the calcium in the adult human body is contained in bones in the form of hydroxyapatite. Children need relatively large amounts of calcium to lay down new bone with rapid growth. It is likely that dietary sources of calcium may be more effective than calcium supplements.

Phosphorus is essential for bone, but too much phosphorus in combination with low calcium intake can lead to reduced calcium bioavailability and potential bone loss. Although uncommon, phosphorus deficiency can lead to reduced mineralization and bone resorption. Deficiency has been seen in older adults with malnutrition, intestinal malabsorption, or long-term use of medications that bind phosphorus, including antacids. In the general population, excess phosphorus is more of a concern than deficiency. The US diet tends to be high in phosphorus relative to calcium. Excess phosphate form complexes with calcium that interfere with calcium absorption, which may in turn lower serum calcium and lead to secretion of parathyroid hormone (PTH), lower 1,25(OH)2D production, lower intestinal calcium absorption and, consequently, bone resorption to release calcium from bone. One major source of excess phosphorus in the US diet is phosphoric acid from cola drinks. Two studies in teenage girls found that cola consumption significantly increased the odds of fracture. In the FOS, women consuming cola daily had significantly lower hip BMD than those who consumed cola less than once per week.

Magnesium is important to the formation of pure hydroxyapatite and may enhance bone strength through its role in crystallization. It also is known to regulate active intestinal calcium transport. In observational studies, magnesium intake was significantly positively associated with BMD, and protective against bone loss. This is important because magnesium intakes tend to be consistently low.

Potassium promotes renal calcium retention and is also important in neutralizing the acid load of most diets, which may protect against calcium loss from the bones. Potassium administration increased serum osteocalcin concentration and decreased urinary hydroxyproline excretion.

Sodium intake in the United States is considerably higher than recommended. Studies have shown that each 1000 mg of additional sodium was associated with a 20-mg increase in urinary calcium loss—the amount likely to be absorbed from 80 mg of dietary calcium, and consequently with lower BMD. The optimal intake balance for protecting bone was approximately 1000 mg calcium and less than 2000 mg sodium per day.

Fluoride has long been known to prevent tooth decay and has been added to most water supplies in the United States. Fluoride substitutes for the hydroxyl group in hydroxyapatite, forming fluorapatite. Fluoride has been shown to result in bone with larger crystals and higher BMD, but lower elasticity.

Iron is an important cofactor for hydroxylases in collagen formation. Both low iron intake and iron overload have been negatively associated with bone. Iron overload has been associated with low BMD in patients with genetic hemochromatosis and with African hemosiderosis. However, low iron is more of a concern in the general population. Rats fed iron-deficient diets showed compromised bone morphology, strength and density, and decreased serum osteocalcin.

Silicon is important for collagen and glycosaminoglycan formation in bone and cartilage, influencing the formation of the organic matrix. Silicon is also a major ion of osteogenic cells. Orthosilicic acid, the form of silicon absorbed in the diet, appears to be associated with bone formation through increased synthesis of collagen type I and stimulation of osteoblasts.

Zinc may affect bone through its role in nucleic acid and protein metabolism. Lower serum and bone zinc and higher urinary zinc have been noted in patients with osteoporosis.

Boron intake may protect bone by decreasing urinary calcium, phosphorus, and magnesium losses and increasing serum estradiol.

Strontium has similarities to calcium, and it has received increasing interest as a treatment for osteoporosis. Doses of 1 to 2 g/day of strontium ranelate for 2 years or longer increased BMD in postmenopausal women by 2% to 3%, relative to placebo, and reduced both vertebral and nonvertebral fracture risk. The increase in BMD is predictable and occurs in all treated individuals because of the ability of strontium to incorporate within the hydroxyapatite crystal. However, fracture risk cannot be predicted based on this increase in BMD.

Manganese also may contribute to bone status, although it has rarely been examined independently from other trace minerals.

Vitamin D (cholecalciferol) promotes positive calcium balance and stimulates bone formation. Hence, it is often considered as a protective vitamin for bone. In the skeleton, activated vitamin D [1,25(OH)2D (calcitriol)] stimulates bone resorption as well as enhances mineralization and bone formation. Vitamin D is obtained from the diet mainly as cholecalciferol (vitamin D3) from animal sources but also as ergocalciferol (vitamin D2) from plant sources. Factors associated with low vitamin D include obesity, older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, and low dietary intake of vitamin D. Dietary intake of vitamin D also has been shown to be protective against fracture.

Vitamin C is an essential cofactor for hydroxylating lysine and proline residues in procollagen.

Vitamin E is a powerful antioxidant and, like vitamin C, may protect against the negative effects of oxidative stress on bone resorption. Bone loss with aging has been associated with prostaglandins, cytokines, and growth factors in the bone microenvironment.

Folate, vitamin B12, and vitamin B6 play important roles in the one-carbon metabolism pathway, which is critical for DNA synthesis, methylation, and repair, and therefore may affect bone formation.

Although vitamin A deficiency is relatively common worldwide, it is retinol excess that is of most concern to bone. Preformed vitamin A is obtained from the diet as retinol and retinyl esters from animal foods and derived from metabolism mainly in the intestine of provitamin A carotenoids.

Carotenoid-rich foods do not contribute to vitamin A toxicity; rather, carotenoids may have a positive effect on bone through their antioxidant activity.       

Metabolic studies have demonstrated that high protein leads to calcium losses, and it has been assumed that calcium is drawn from the skeleton to maintain serum calcium concentrations in the face of an acid load.

Fatty acids are important to numerous aspects of metabolism. The n-3 and n-6 polyunsaturated fatty acids may influence bone health through several complex mechanisms, including opposing effects on inflammatory cytokines, modulation of prostaglandin E2 production, and enhancement of calcium transport and retention.

Some evidence shows that caffeine has a negative effect on bone, although study results vary.

Osteoporosis is commonly seen in chronic alcoholism. Heavy use of alcohol is associated with multiple nutritional deficiencies which are likely to have their own negative effects on bone. In addition, ethanol itself appears to have direct effects on bone remodeling, affecting both BMD and bone strength. Long-term administration (3 months) of alcohol at a dose roughly equivalent to 1 L of wine per day in male adult rats showed a 10% reduction in bone density and a 12% reduction of mechanical strength of the femur.

Numerous studies show that higher total body weight is directly associated with greater BMD and lower risk of fracture. Further, weight loss is associated with loss in BMD.

Many aspects of diet and nutrition are important for bone health, including not only adequate intake of calcium and vitamin D but also of magnesium, potassium, other trace minerals, vitamin K, B vitamins, carotenoids, vitamins C and E, protein, and essential fatty acids. At the same time, it is important to avoid excess intakes of phosphorus, vitamin A, and sodium, and to maintain moderate alcohol intake. Although osteoporosis is one area in which BMI has been shown to be protective, we now understand that abdominal adiposity can have negative effects on bone through the release of certain cytokines. Weight-bearing physical activity is protective and is particularly important during weight loss, which may otherwise lead to bone loss as well. Musclestrengthening exercises also can help to protect against weight loss–associated bone loss and help to strengthen muscles to reduce the risk of falling. Increased muscle mass also may contribute to greater bone strength among individuals across all age groups.