This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age. For vitamin D, RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter), meet the requirements of at least 97.5% of the population. RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer. Higher values were not consistently associated with greater benefit, and for some outcomes U-shaped associations were observed, with risks at both low and high levels. The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated. Urgent research and clinical priorities were identified, including reassessment of laboratory ranges for 25-hydroxyvitamin D, to avoid problems of both undertreatment and overtreatment.

It is well-recognized that young women with untreated premature ovarian failure (POF) are at increased risk of osteoporosis and bone fracture. Large, randomized trials have demonstrated that hormone replacement therapy with estrogen/progesterone in postmenopausal women can dramatically improve bone mineral density (BMD) and reduce fracture risk; however, there are little data on the effect of hormone replacement in young women with POF. At present, young women with POF are given either combined hormone replacement treatment or physiologic SSR (pSSR) consisting of combined transdermal estradiol and vaginal progesterone replacement regimens.This open-label, randomized controlled crossover pilot trial was designed to determine whether a regimen of pSSR could improve skeletal health among young women with POF caused by a variety of reasons. A total of 34 patients were randomized to receive a 4-week cycle of either pSSR (transdermal estradiol 100 g daily for week 1 and 150 g for weeks 2-4, with progesterone 200 mg twice daily for weeks 3-4) or standard hormone replacement therapy (sHRT) (oral ethinyl estradiol 30 g and norethisterone 1.5 mg daily for weeks 1-3, followed by 7 "pill-free" days for 12 months). Dual-energy x-ray absorptiometry was used to measure BMD at baseline and after each 12-month treatment period. During the study period, blood samples were collected for hormonal measurements and for markers of bone formation (bone alkaline phosphatase and procollagen type I aminoterminal propeptide) and bone resorption (CrossLaps [cross-linked C-terminal telopeptide of type I collagen]) before and after each washout period, and at 3, 6, and 12 months. Of the 34 women, 18 (mean age 27; range, 19-39 years) completed the study. LH (luteinizing hormone) and FSH (follicle-stimulating hormone) were decreased to a similar extent by both pSSR and sHRT. Treatment with pSSR increased the mean baseline lumbar spine BMD z-score by ϩ0.17 (95% confidence interval: ϩ0.07 to ϩ0.27; P ϭ 0.003), whereas there was no significant increase in response to sHRT (ϩ0.07, with a 95% confidence interval: Ϫ0.03 to ϩ0.18; P ϭ 0.2). During pSSR, the increment in lumbar spine BMD z-score was positively associated with estradiol (r ϭ ϩ0.49; P ϭ 0.04) and inversely associated with FSH (r ϭ Ϫ0.65; P ϭ 0.004). Both bone alkaline phosphatase and procollagen type I amino-terminal propeptide were increased significantly by pSSR ( ANOVA P Ͻ 0.001). In contrast, both of these bone formation markers were decreased by sHRT (P Ͻ 0.01). The bone resorption marker, CrossLaps, was suppressed by both regimens (P Ͻ 0.001). GYNECOLOGYVolume 66, Number 6 OBSTETRICAL AND GYNECOLOGICAL SURVEY

Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture.

Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity.

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