Body composition and bone mineral density after ovarian hormone suppression with or without estradiol treatment.

OBJECTIVE: Suppression of ovarian hormones in premenopausal women on gonadotropin-releasing hormone agonist (GnRH(AG)) therapy can cause fat mass (FM) gain and fat-free mass (FFM) loss. Whether this is specifically caused by a decline in serum estradiol (E2) is unknown. This study aims to evaluate the effects of GnRH(AG) with placebo (PL) or E2 add-back therapy on FM, FFM, and bone mineral density (BMD). Our exploratory aim was to evaluate the effects of resistance exercise training on body composition during the drug intervention. METHODS: Seventy healthy premenopausal women underwent 5 months of GnRH(AG) therapy and were randomized to receive transdermal E2 (GnRH(AG) + E2, n = 35) or PL (GnRH(AG) + PL, n = 35) add-back therapy. As part of our exploratory aim to evaluate whether exercise can minimize the effects of hormone suppression, some women within each drug arm were randomized to undergo a resistance exercise program (GnRH(AG) + E2 + Ex, n = 12; GnRH(AG) + PL + Ex, n = 12). RESULTS: The groups did not differ in mean (SD) age (36 [8] and 35 [9] y) or mean (SD) body mass index (both 28 [6] kg/m). FFM declined in response to GnRH(AG) + PL (mean, -0.6 kg; 95% CI, -1.0 to -0.3) but not in response to GnRH(AG) + E2 (mean, 0.3 kg; 95% CI, -0.2 to 0.8) or GnRH(AG) + PL + Ex (mean, 0.1 kg; 95% CI, -0.6 to 0.7). Although FM did not change in either group, visceral fat area increased in response to GnRH(AG) + PL but not in response to GnRH(AG) + E2. GnRH(AG) + PL induced a decrease in BMD at the lumbar spine and proximal femur that was prevented by E2. Preliminary data suggest that exercise may have favorable effects on FM, FFM, and hip BMD. CONCLUSIONS: Suppression of ovarian E2 results in loss of bone and FFM and expansion of abdominal adipose depots. Failure of hormone suppression to increase total FM conflicts with previous studies of the effects of GnRH(AG). Further research is necessary to understand the role of estrogen in energy balance regulation and fat distribution.

Managing osteoporosis in postmenopausal women.

PURPOSE: To describe strategies used in managing postmenopausal osteoporosis, including a bone-healthy lifestyle, adequate calcium and vitamin D intake, and drug therapy options; considerations in selecting osteoporosis drug therapy; and the role of health-system pharmacists in managing osteoporosis in postmenopausal women. SUMMARY: Postmenopausal women are at risk for osteoporosis and fractures. Weight-bearing and resistance exercise, limiting alcohol and caffeine intake, smoking cessation, and fall prevention strategies are part of a bone-healthy lifestyle used to manage postmenopausal osteoporosis. Supplements containing calcium and vitamin D are needed by many postmenopausal women because of an inadequate intake and other factors. The choice of osteoporosis drug therapy should take into consideration patient characteristics and preference and drug efficacy, safety, route of administration, dosing frequency, convenience, cost, and potential for nonadherence. Bisphosphonates generally are preferred for the prevention and treatment of osteoporosis in postmenopausal women, with raloxifene, teriparatide, and calcitonin salmon as alternatives. Denosumab, a fully human monoclonal immunoglobulin G(2) antibody, may become available soon for prevention and treatment of postmenopausal osteoporosis. Health-system pharmacists can improve the management of osteoporosis in postmenopausal women by counseling them on a bone-healthy lifestyle and making recommendations for calcium and vitamin D supplements and osteoporosis medications to prevent or treat the disease. CONCLUSION: A variety of approaches are available to promote bone health in postmenopausal women. Health-system pharmacists can promote interventions to optimize patient outcomes.

The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease.

Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD). Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking. The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD. This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center. Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry. Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%). On bivariate analysis, there was no association between TNF-alpha and BMD. Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density. However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability. Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis. The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis. We conclude that the effect of adipokines on BMD does not appear to be independent of body mass. However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD.

Diagnosis and management of osteoporosis in the older senior.

The older senior is at high risk for osteoporosis. It is important for healthcare providers to be fully aware of the potential risks and benefits of diagnosing and treating osteoporosis in the older senior population. Data indicate that bone mineral density testing is under-utilized and drug therapy is often not initiated when indicated in this population. Bone mineral density testing with central dual energy x-ray absorptiometry is essential and cost-effective in this population. All older seniors should be educated on a bone-healthy lifestyle including age-appropriate weight-bearing exercise and smoking cessation if necessary. It is important to remember that falls play a very important role in the risk for osteoporotic fractures, especially in the older senior. All older seniors should be evaluated annually for falls and strategies should be implemented to reduce fall risk in this population. The risk for vitamin D insufficiency and deficiency is high in the older senior and can contribute to falls and fractures. Adequate intakes of calcium and vitamin D are important and deficiencies need to be treated. Data on osteoporosis drug therapy in the older senior are lacking. Based on data from subgroup analyses of large osteoporosis trials in postmenopausal women, current osteoporosis therapies appear safe and efficacious in the older senior and most will live long enough to derive a benefit from these therapies. Further studies are needed in older seniors, especially men, to better understand the risks and benefits of pharmacologic therapy for the management of osteoporosis.

Osteoporosis risk in premenopausal women.

Although clinically significant bone loss and fractures in healthy premenopausal women are rare, more women are seeking evaluation for osteoporosis from their health care providers. As pharmacists are in an ideal position to influence the management of premenopausal women with osteoporosis, it is important that pharmacists understand the available data on bone loss, fractures, and risk factors and secondary causes for osteoporosis, as well as when to recommend testing and treatment in premenopausal women. Limited data are available; therefore, we conducted a MEDLINE search of the literature from January 1993-August 2008. Studies evaluating bone loss, fractures, and fracture risk in healthy premenopausal women were targeted and summarized; most recommendations are based on expert opinion. A small but statistically significant loss in bone mineral density of 0.25-1%/year by dual-energy x-ray absorptiometry is seen healthy premenopausal women; the clinical significance of this is unknown. Whereas absolute fracture risk is low, premenopausal fractures appear to increase postmenopausal fracture risk by 1.5-3-fold. Risk factors for low bone density appear to be similar between pre- and postmenopausal women. Bone density screening in healthy premenopausal women is not recommended, but bone mineral density testing is advisable for those who have conditions or who receive drug therapy that may cause secondary bone loss. Lifestyle modification emphasizing bone-healthy habits such as adequate calcium and vitamin D nutrition, regular exercise, limitation of caffeine and alcohol consumption, and avoidance of tobacco are essential to the management of osteoporosis risk. The efficacy and safety of osteoporosis drugs have not been adequately demonstrated in premenopausal women. Therefore, pharmacologic interventions cannot be recommended in young women with low bone mass but may be considered in those having a more significant fracture risk, such as those with a previous low-trauma fracture or an identified secondary cause for bone loss.