Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss.

CONTEXT: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. OBJECTIVE: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. DESIGN: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. SETTING: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). PARTICIPANTS: Participants included 186 postmenopausal women aged 40-65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5. INTERVENTION: Women, stratified by lumbar T-score (<-1.50 and >or=-1.50) and years since menopause (5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. MEASUREMENTS: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. RESULTS: After 36 months of therapy, changes of -2.1% in the active group (n = 88) and -2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval -1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different. CONCLUSIONS: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only approximately 16 mg/d); a sub-therapeutic dose.

Breastfeeding and postmenopausal osteoporosis.

Bone loss associated with osteoporosis occurs with high frequency among the elderly and often results in debilitating fractures. A combination of lifestyle behaviors, genetic predisposition, and disease processes contributes to bone metabolism. Therefore, any discussion regarding bone health must address these factors. The impact of menopause on bone turnover has been generally well studied and characterized. Breastfeeding places significant stress on calcium metabolism and, as a consequence, directly influences bone metabolism. The most significant factors affecting bone mineral density (BMD) and bone metabolism are the duration and frequency of lactation, the return of menses, and pre-pregnancy weight. Although transient, lactation is associated with bone loss. As clinical guidelines and public health policies are being formulated, there is a compelling need for further investigation into the relationship of lactation, BMD, and subsequent risk of osteoporosis. Better understanding of this relationship will provide new opportunities for early intervention and ultimately help in the prevention of bone loss in postmenopausal women.

The effects of time-to-surgery on mortality and morbidity in patients following hip fracture.

PURPOSE: There is a perception that the standard of care is to repair hip fractures surgically within 24 hours of hospitalization. However, it is unclear whether this reduces mortality or morbidity. SUBJECTS AND METHODS: We performed a retrospective study in consecutive hip fracture patients, aged 60 years or older, who underwent surgical repair. Patients with metastatic cancer, trauma, or a fracture occurring >48 hours before admission were excluded. The primary outcome was long-term (up to 18 years) mortality. Secondary outcomes included 30-day mortality and decubitus ulcers, serious bacterial infections, myocardial infarction, and thromboembolism. Analyses were adjusted for medical conditions; the comparison group comprised patients who underwent surgery for hip fracture repair within 24 to 48 hours because there were no patients with active medical problems who underwent surgery within 24 hours. RESULTS: Of the 8383 patients, surgery was delayed for more than 24 hours in 2464 patients (29%) for medical reasons and in 1341 patients (16%) without active medical problems. Compared with those who underwent surgery 24 to 48 hours after admission to the hospital, patients who underwent surgery more than 96 hours after admission did not have increased long-term mortality (hazard ratio = 1.07; 95% confidence interval [CI]: 0.95 to 1.21), although the risk of decubitus ulcer was increased (odds ratio = 2.2; 95% CI: 1.6 to 3.1). There were no associations between time-to-surgery and the other secondary outcomes. CONCLUSION: Time-to-surgery in hip fracture patients was not associated with short- or long-term mortality after adjusting for active medical problems. Other than increasing the risk of decubitus ulcer formation, waiting did not appear to affect patients' outcomes adversely.