The FDA is requiring a boxed warning in the label of denosumab (Prolia – Amgen), a monoclonal antibody that inhibits osteoclasts, about an increased risk of severe hypocalcemia in patients with advanced chronic kidney disease (CKD; eGFR <30 mL/min/1.73 m²), particularly those on dialysis. FDA-approved indications for Prolia are listed in Table 1.

US guidelines recommend pharmacologic therapy for postmenopausal women with a bone density T-score (standard deviation from normal mean values in healthy young women) of -2.5 or below in the lumbar spine, femoral neck, total hip, or distal radius, a T-score between -1.0 and -2.5 and a history of fragility (low-trauma) fracture of the hip or spine, or a T-score between -1.0 and -2.5 and a FRAX 10-year probability of ≥3% for hip fracture or ≥20% for major osteoporotic fracture (hip, clinical spine, humerus, distal radius).

Gastroesophageal reflux disease (GERD) is the most frequent GI condition encountered in the outpatient setting; it affects about 20% of the US population. Heartburn and regurgitation are the classic symptoms of GERD.

Diagnosis of osteoporosis is based on the results of bone mineral density (BMD) testing or by the occurrence of a fragility fracture. Bone densitometry results are generally reported in terms of standard deviations (SD) from the mean value for young adults (T-score). The World Health Organization (WHO) defines osteoporosis in women as a T-score of -2.5 or below in the spine, femoral neck, or total hip. A computerized model (FRAX) is available that estimates the 10-year probability of a hip fracture or other major osteoporotic fracture based on clinical risk factors and BMD at the femoral neck.

Primary hypothyroidism is usually the result of Hashimoto's thyroiditis, thyroidectomy, or radioactive iodine therapy. Treatment of hypothyroidism with replacement doses of thyroid hormone is usually lifelong. Levothyroxine is the drug of choice.

The FDA has approved a subcutaneously injected formulation of recombinant human parathyroid hormone (Natpara – NPS) as an adjunct to calcium and vitamin D to control hypocalcemia in adults with hypoparathyroidism. Natpara is an 84-amino acid single-chain polypeptide identical to native parathyroid hormone. It is the first parathyroid hormone formulation to be approved for this indication.

US guidelines for the treatment of osteoporosis have been published. The diagnosis of osteoporosis has traditionally been established by the occurrence of fragility fractures or by bone densitometry, which is generally reported in terms of standard deviations (SD) from mean values in young adults (T-score). The World Health Organization (WHO) has defined normal bone mineral density (BMD) for women as a value within one SD of the young adult mean. Values 2.5 SD or more below the mean (T-score -2.5 or below) at the spine, femoral neck, or total hip are defined as osteoporosis. The WHO has developed a computerized model (FRAX) that predicts the 10-year probability of a hip fracture or other major osteoporotic fracture based on clinical risk factors and BMD at the femoral neck.

The US Preventive Services Task Force (USPSTF) has issued a Draft Recommendation Statement saying, in effect, that community-dwelling women and men should not take calcium and vitamin D supplements for primary prevention of osteoporotic fractures because the evidence that they are helpful is insufficient and they increase the risk of kidney stones. The Medical Letter has said previously that there is no evidence that patients with an adequate intake of calcium (1000-1200 mg/day) and vitamin D (600-800 IU/day) will benefit from taking supplements.1

1. Drugs for postmenopausal osteoporosis. Treat Guidel Med Lett 2011; 9:67.

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Osteoporosis is characterized by low bone mass with microarchitectural disruption and skeletal fragility that results in an increased risk of fracture. The diagnosis has traditionally been established by bone densitometry, which is generally reported in terms of standard deviations (SD) from mean values in young adults (T-score). The World Health Organization (WHO) has defined normal bone mineral density (BMD) for women as a value within one SD of the young adult mean. Values 2.5 SD or more below the mean (T score -2.5) are defined as osteoporosis. The WHO has developed a computerized model (FRAX) that predicts the 10-year probability of a hip fracture or any other major osteoporotic fracture based on clinical risk factors and BMD at the femoral neck.

Supplemental calcium is recommended for prevention of postmenopausal osteoporosis in women with an inadequate dietary intake of calcium. The safety of calcium supplements has recently been questioned; patients may ask if they should continue to take them. The source of this concern was the publication of 2 meta-analyses in the British Medical Journal.

The results of a randomized, placebo-controlled trial of calcium and vitamin D supplements in more than 36,000 postmenopausal women, conducted as part of the Women’s Health Initiative (RD Jackson et al. N Engl J Med 2006; 354:669), have been misinterpreted by some patients to mean that they should stop taking such supplements.

At the time of recruitment, the participants in this study had an average daily calcium intake of 1100-1200 mg. They were randomized to take either 1000 mg of calcium carbonate plus 400 IU of vitamin D₃ or a placebo for an average of 7 years. Both groups were permitted to take calcium and vitamin D supplements on their own as well. In the intention-to-treat population, the study supplements increased hip bone density but did not decrease the incidence of hip fractures. The subgroup of women who adhered to the protocol and actually took the study supplements showed a significant reduction in hip fractures compared to the control group.

Men and women over age 50 should have a total calcium intake of about 1200 mg per day (Treat Guidel Med Lett 2005; 3:69). If they need a supplement to achieve that, calcium citrate is more expensive, but it offers some advantages over calcium carbonate: it can be taken without food, causes less GI disturbance and may be less likely to cause kidney stones.

With any calcium salt, vitamin D is necessary for optimal absorption. The recommended minimum daily requirement of vitamin D (vitamin D₃ is preferred) is 400 IU for people 50-70 years old and 600 IU for those over 70. But those infrequently exposed to the sun may need 800- 1000 IU of vitamin D daily, and many experts recommend 800 IU or more for all postmenopausal women.

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Claims for the superiority of various calcium supplements are now appearing on television and in the print media. A high calcium intake combined with vitamin D can increase bone density and reduce the incidence of fractures in older women and probably also in men.

Many different calcium supplements are promoted for prevention of postmenopausal osteoporosis. Whether a lifelong increase in calcium intake decreases the risk of osteoporosis is unclear, but the results of some clinical trials suggest that it might. Calcium supplementation increased bone mineral density in children and adolescents and, started a few years after menopause, decreased bone loss in postmenopausal women (CC Johnston, Jr et al, N Engl J Med, 327:82, 1992; T Lloyd et al, JAMA, 270:841, 1993; IR Reid et al, AM J Med, 98:331, 1995). Elderly women who took calcium and vitamin D supplements had a lower incidence of hip fractures than those who took placebo (MC Chapuy et al. N Engl J Med, 327:1637, 1992)

Whether a lifelong increase in calcium intake can prevent osteoporosis remains controversial, but many women are now taking calcium supplements on the chance that it might. The typical diet of women in the USA includes less than 600 mg of calcium per day. The National Research Council (NRC) recommends a calcium intake of 1200 mg daily from adolescence through age 24, and 800 mg daily thereafter (Food and Nutrition Board, NRC, Recommended Dietary Allowances, 10th ed, Washington, DC:National Academy Press, 1989, p 174). For mature women, some Medical Letter consultants recommend daily calcium intakes of 1000 mg before menopause and 1500 mg afterward. The effectiveness of estrogen replacement at menopause in preventing postmenopausal bone loss is no longer controversial, and the results of one study suggested that calcium supplementation can lower the effective dosage of estrogen (Committee on Diet and Health, NRC, Diet and Health, Washington, DC:National Academy Press, 1989, p 347).