Is poor nutrition masking the effects of depomedroxyprogesterone acetate on bones in adolescent users?

INTRODUCTION: Research in the developed countries has documented bone loss in adolescents who use depomedroxyprogesterone acetate (DMPA) as a contraceptive for less than two years. DMPA use often begins during adolescence in Bangladesh, a South Asian developing country, where more than 50% of women are undernourished. Poor nutrition is also associated with low bone mineral density (BMD) in South Asian women. We investigated the effects of long-term (two or more years) DMPA use on BMD in Bangladeshi women who started its use in their adolescence. METHODS: Lumbar spine and femur neck BMD were acquired using dual energy X-ray absorptiometry for 100 adolescents (50 DMPA users and 50 non-users) in a cross-sectional study in Dhaka, Bangladesh. Multivariate analysis was used to determine the associations between BMD and DMPA use. Stratified analysis of DMPA use investigated the determinants of BMD in both groups. RESULTS: The participants (mean age 18 +/- 2 years) were generally below their ideal body weight. No significant differences in BMD were found between the two groups. Weight (odds ratio [OR] 0.96, 95 percent confidence interval [CI], 0.92-1.00) and height (OR 0.68, 95 percent CI 0.49-0.94) were independent determinants (p-value is less than 0.05) of lumbar and femur neck BMD, respectively. CONCLUSION: Poor nutritional status, indicated by a less-than-ideal body weight, may be masking the effects of DMPA on bone loss among adolescent users. Our findings suggest that nutritional supplementation may be required with DMPA prescription to promote bone health in adolescent users who are approaching peak bone mass.

Recovery of spaceflight-induced bone loss: bone mineral density after long-duration missions as fitted with an exponential function.

The loss of bone mineral in NASA astronauts during spaceflight has been investigated throughout the more than 40 years of space travel. Consequently, it is a medical requirement at NASA Johnson Space Center (JSC) that changes in bone mass be monitored in crew members by measuring bone mineral density (BMD), with dual-energy X-ray absorptiometry (DXA) before and after flight, of astronauts who serve on long-duration missions (4-6 months). We evaluated this repository of medical data to track whether there is recovery of bone mineral that was lost during spaceflight. Our analysis was supplemented by BMD data from cosmonauts (by convention, a space traveler formally employed by the Russia Aviation and Space Agency or by the previous Soviet Union) who had also flown on long-duration missions. Data from a total of 45 individual crew members - a small number of whom flew on more than one mission - were used in this analysis. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing). Plotted BMD changes were fitted to an exponential mathematical function that estimated: (i) BMD change on landing day (day 0) and (ii) the number of days after landing when 50% of the lost bone would be recovered ("50% recovery time") in the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. In sum, averaged losses of bone mineral after long-duration spaceflight ranged between 2% and 9% across all sites with our recovery model predicting a 50% restoration of bone loss for all sites to be within 9 months.

Skeletal responses to space flight and the bed rest analog: a review.

The potential for loss of bone mineral mass due to space flight was recognized by space scientists even before man's first venture into micro-gravity. Early life science studies in both the U.S. and Russian space programs attempted to measure the effects of reduced gravity on skeletal homeostasis, and these measurements have become more sophisticated with time. Bone-related measurements have typically included: bone mineral density measured by X-ray absorptiometry and more recently CT scanning; bonerelated hormones and other biochemical markers of bone turnover; and calcium excretion and balance. These measurements, conducted over the last 4 decades, have shed light on the nature of disuse bone loss and have provided preliminary information regarding bone recovery. Ground-based analog (bed rest) studies have provided information complementary to the space flight data and have allowed the testing of various countermeasures to bone loss. In spite of the wealth of knowledge obtained thus far, many questions remain regarding bone loss, bone recovery, and the factors affecting these skeletal processes. This paper will summarize the skeletal data obtained to date by the U.S. and Russian space programs and in ground-based disuse studies. In addition, related body composition data will be briefly discussed, as will possible countermeasures to space flight-induced bone loss.

Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy.

The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.

Eddy current correction in volume-localized MR spectroscopy.

The quality of volume-localized magnetic resonance spectroscopy is affected by eddy currents caused by gradient switching. Eddy currents can be reduced with improved gradient systems; however, it has been suggested that the distortion due to eddy currents can be compensated for during postprocessing with a single-frequency reference signal. The authors propose modifying current techniques for acquiring the single-frequency reference signal by using relaxation weighting to reduce interference from components that cannot be eliminated by digital filtering alone. Additional sequences with T1 or T2 weighting for reference signal acquisition are shown to have the same eddy current characteristics as the original signal without relaxation weighting. The authors also studied a new eddy current correction method that does not require a single-frequency reference signal. This method uses two free induction decays (FIDs) collected from the same volume with two sequences with opposite gradients. Phase errors caused by eddy currents are opposite in these two FIDs and can be canceled completely by combining the FIDs. These methods were tested in a phantom. Eddy current distortions were corrected, allowing quantitative measurement of structures such as the -CH = CH- component, which is otherwise undetectable.

Effects of weight lifting on bone mineral density in premenopausal women.

A group of 68 premenopausal women participated in a controlled 12 month exercise program. Two groups were matched according to age, body size (body mass index), and typical activity level. Data collection included bone mineral density (BMD) of the lumbar spine with dual-photon absorptiometry and of the os calcis with single-photon absorptiometry, lean body mass, urinary calcium/creatinine, and urinary gamma-carboxyglutamic acid (Gla). Subjects were given a daily 500 mg supplement of elemental calcium. There was no significant difference between groups in terms of diet, in urinary calcium/creatinine or Gla, or in lean body mass. The weight lifting group had a nonsignificant increase in mean lumbar BMD of 0.81% and the control group exhibited a nonsignificant decrease of 0.5%. However, a paired t-test revealed a significant change in the means in either group or as matched pairs. The relatively small change seen as a result of this modified Nautilus exercise program may prevent moderate weight lifting from being a practical answer for osteoporosis, even in a highly motivated population.

Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate.

We have designed a cyclic regimen for the treatment of osteoporosis based on the activate, depress, free, and repeat (ADFR) concept. Osteoclastic bone resorption is activated by 7 days of oral neutral phosphate and inhibited with a brief pulse (5 days) of etidronate disodium at a high dose (20 mg/kg body weight). Patients next take calcium supplements for 48 days before resuming phosphate to enter the next cycle. Osteoporotic women increased the bone mineral density of the lumbar spine at 6 months by 7.2 +/- 5.2% (mean +/- SD, N = 14) and at 12 months by 8.2 +/- 4.0% (N = 8). Control observations in regularly exercising postmenopausal women (N = 30) showed no significant change in spine mineral density after 20 months (0.5 +/- 3.2%), confirming the stability of the measurement technique. The two patients who responded poorly to the cyclic regimen each showed a blunted rise in serum PTH during oral phosphate administration, suggesting that the rise in PTH induced by oral phosphate may be an important component of this cyclic regimen. This preliminary study does not identify which component or components of the regimen are responsible for the increase in bone mass but provides positive encouragement for randomized studies designed to determine the optimum dosage, duration, and timing of each component of the regimen.

Bone mineral content reflects total body calcium in neonatal miniature piglets.

We measured bone mineral content (BMC) in 18 neonatal miniature piglets by single photon absorptiometry, total body calcium (TBC) by total body neutron activation analysis, growth, and serum indices of mineral status (calcium, phosphorus, alkaline phosphatase activity). Measurements were begun on day 6, when the piglets were weaned, and were continued to day 19. After weaning, the piglets were assigned randomly to receive one of three diets which differed only in their concentrations of calcium and phosphorus: 100% of the recommended level (diet A), 60% (diet B), and 20% (diet C). No differences were observed among groups during the 19-day study, either in weight gain (48 +/- 2 g/day) or increment in crown-rump length (2.4 +/- 0.2 cm/wk). BMC correlated significantly (p less than 0.001) with TBC at 6 (r = 0.83), 13 (r = 0.77), and 19 (r = 0.93) days. BMC correlated significantly (p less than 0.001) with the ash weight (r = 0.87) and calcium content (r = 0.90) of the corresponding tibial bone segment. Anthropometric parameters and serum indices of mineral status did not predict TBC as accurately as did BMC measurements. We observed a range in BMC measurements in this study that was similar to the range reported for infants in the 1st yr of life. The high correlation between BMC and TBC suggested that BMC is useful in the assessment of mineral status in infants.

Zinc, copper, and nitrogen balances during bed rest and fluoride supplementation in healthy adult males.

The effects of bed rest and fluoride supplementation on zinc, copper, and nitrogen balances and Zn and Cu serum levels were measured in 15 healthy males. Subjects aged 19-54 y remained on a metabolic research ward for 10 wk. During weeks 1-5, subjects were ambulatory. During wks 6-10 they remained in continuous bed rest. During weeks 3-10 nine subjects received 10 or 20 mg F/d as sodium fluoride. Daily urine and weekly fecal composites were made and biweekly fasting blood samples were taken. Dietary intakes were 1.40 +/- 0.17 mg Cu/d (22.0 +/- 2.7 mumol Cu/d), 10.82 +/- 0.49 mg Zn/d (165.6 +/- 7.6 mumol Zn/d), and 14.27 +/- 0.23 g N/d (1019 +/- 16 mmol N/d). Bed rest increased urinary Zn and N excretions and fecal Zn excretions and decreased Zn balance (p less than 0.05) whereas Cu balance was unchanged. During bed rest, F supplementation increased Zn and N balances compared with untreated control subjects (p less than 0.05). These results are compatible with bone and muscle atrophy during bed rest and increased bone formation with F supplementation.