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Background: It is unclear why some adolescents experience substantial bone mineral density (BMD) loss, while others experience a minimal decrease during depot medroxyprogesterone acetate (DMPA) use. We examined biopsychosocial factors in adolescents who experienced ≥5% BMD loss from baseline compared with adolescents who experienced <5% BMD loss during DMPA use., Study Design: A multicenter, prospective, nonrandomized study of 181 female adolescents who initiated DMPA for contraception was conducted. BMD (by dual-energy X-ray absorptiometry) and serum estradiol were measured at initiation and every 6 months for 240 weeks of DMPA use., Results: Half of participants experienced BMD loss of ≥5% from baseline at the hip, and a quarter experienced BMD loss of ≥5% at the lumbar spine (BMD substantial losers, SL). Hip and lumbar spine BMD-SL received a significantly greater number of DMPA injections than non-SL (p<.001). Decreased estradiol levels did not statistically differ between BMD loss subgroups. Hip BMD-SL had significantly lower baseline body mass index (BMI) than non-SL (p=.002), and there was an inverse relationship between weight gain and degree of BMD loss. Mean calcium intake was significantly lower (p<.05) in hip BMD-SL, and reported alcohol use was significantly higher (p<.05) in lumbar spine BMD-SL compared with non-SL., Conclusions: BMD loss of ≥5% was more common at the hip than at the lumbar spine among adolescents using DMPA. Decreased serum estradiol levels did not correlate with magnitude of BMD loss. Lower BMI and calcium intake and greater alcohol use were associated with greater BMD loss in adolescents using DMPA., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Depot medroxyprogesterone acetate (DMPA) is a highly effective progestin-only contraceptive that is widely used by adolescents. We investigated bone mineral density (BMD) changes in female adolescents during and following use of this method., Study Design: A multicenter, prospective, non-randomized observational study in 98 healthy female adolescents aged 12-18 years who initiated DMPA intramuscular injections for contraception and provided BMD data for up to 240 weeks while receiving DMPA and for up to 300 weeks after DMPA cessation. BMD at the lumbar spine (LS), total hip (TH) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry. A mixed model analysis of variance was used to examine BMD changes., Results: At the time of their final DMPA injection, participants had mean BMD declines from baseline of 2.7% (LS), 4.1% (TH) and 3.9% (FN) (p<.001 at all three sites). Within 60 weeks of discontinuation of DMPA, mean LS BMD had returned to baseline levels, and 240 weeks after DMPA discontinuation, the mean LS BMD was 4.7% above baseline. Mean TH and FN BMD values recovered to baseline values more slowly: 240 weeks and 180 weeks, respectively, after the last DMPA injection., Conclusions: BMD loss in female adolescents receiving DMPA for contraception is substantially or fully reversible in most girls following discontinuation of DMPA, with faster recovery at the LS than at the hip., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To determine whether bone mineral density (BMD) is lower in hormonal-contraceptive users than in an untreated comparison group., Design: Observational, prospective cohort; 24-month duration., Setting: Adolescent clinics in a metropolitan Midwestern setting., Patient(s): Four hundred thirty-three postmenarcheal girls, 12-18 years of age, who were on depot medroxyprogesterone acetate (DMPA; n = 58), were on oral contraceptives (OCs; n = 187), or were untreated (n = 188)., Intervention(s): Depot medroxyprogesterone acetate and OCs containing 100 microg of levonorgestrel and 20 microg of ethinyl E(2)., Main Outcome Measure(s): Measurements of BMD at spine and femoral neck were obtained by using dual x-ray absorptiometry at baseline and 6-month intervals., Result(s): Over 24 months, mean percentage change in spine BMD was as follows: DMPA, -1.5%; OC, +4.2%; and untreated, +6.3%. Mean percentage change in femoral neck BMD was as follows: DMPA, -5.2%; OC, +3.0%; and untreated, +3.8%. Statistical significance was found between the DMPA group and the other two groups. In the DMPA group, mean percentage change in spine BMD over the first 12 months was -1.4%; the rate of change slowed to -0.1% over the second 12 months. No bone density loss reached the level of osteopenia., Conclusion(s): Adolescent girls receiving DMPA had significant loss in BMD, compared with bone gain in the OC and untreated group. However, the clinical significance of this finding is mitigated by slowed loss after the 1st year of DMPA use and general maintenance of bone density values within the normal range in the DMPA group.

Background: This analysis was conducted to assess the baseline data and design methodology within an observational longitudinal comparison of use vs. nonuse of the injectable (intramuscular) contraceptive depot medroxyprogesterone acetate (DMPA-IM) and its effect on bone mass in adolescent women., Study Design: A prospective, observational, open-label, unmatched-cohort, safety study in females aged 11-18 years. Participants either self-selected DMPA-IM (Depo-Provera) 150 mg to be administered every 12 weeks for up to 240 weeks with a 120-week post-treatment follow-up or were nonusers (users of nonhormonal contraception or sexually abstinent) who were to be followed up for up to 360 weeks. As each participant entered the study, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine, hip and femoral neck regions, along with total body bone mineral content; serum and urine specimens were obtained for assay of bone metabolism markers and participants' histories of parity and tobacco and alcohol use were obtained., Results: A total of 389 participants were enrolled: 169 elected to begin DMPA-IM; 26 chose nonhormonal methods and 194 were abstinent. The baseline characteristics indicated significant disparities between DMPA-IM users and nonusers: compared with the nonusers, DMPA-IM users had more advanced chronologic and gynecologic ages, were more likely to have smoked, been pregnant and included more blacks. These factors would likely influence bone accretion rates independent of DMPA-IM exposure. Comparison of participant BMDs with standard reference data revealed that the study cohorts did not match reference populations closely enough to make a direct between-cohort comparative analysis feasible., Conclusions: The baseline differences in cohort characteristics preclude a meaningful comparison of mean BMD changes over time between DMPA-IM users and nonusers cohorts, and comparisons of changes in Z-scores between cohorts were also not appropriate. Therefore, within-participant BMD decreases from baseline were established as safety thresholds, and the proportion of individuals crossing those thresholds on a persistent or progressive basis was identified as the revised primary end point.

Purpose: During adolescence, bone formation prevails over resorption, resulting in accumulation of 40% of peak bone mass throughout this time period. Although multiple studies have explored bone mass accrual during the early stages of puberty, less is known about factors that may influence bone accrual during later years of adolescence. In the present cross-sectional study we examined relationships among bone mineral density (BMD) and demographic factors, behavioral variables, and bone metabolism markers in postmenarchal adolescent girls., Methods: The population was comprised of 389 healthy postmenarchal adolescent girls aged 11-18 years, who were recruited into a prospective study of the effect of depot medroxyprogesterone acetate (DMPA) on bone health in adolescents. At the baseline visit, investigators collected demographic, reproductive health, and lifestyle data, and performed a complete physical examination. Body mass index (BMI) was calculated. Before study initiation, BMD at the lumbar spine, total hip, and femoral neck was measured by dual-energy X-ray absorptiometry (DXA), and markers of bone metabolism (serum bone-specific alkaline phosphatase [BAP], serum osteocalcin, and urinary N-telopeptide [uNTX]) were measured. The baseline data from this study were analyzed to evaluate possible correlates of BMD in postmenarchal adolescent girls. Potential associations between BMD values and other parameters were assessed by analysis of variance and Pearson's correlation coefficient., Results: Participants enrolled in the study had a mean (+/- SD) chronological age of 14.9 +/-1.7 years (range 11-18), mean gynecologic age of 39.9 +/-23.0 months (range 1-120) postmenarche, and mean BMI of 23.5 +/-4.6 kg/m(2) (range 16.0-42.2). Racial/ethnic distribution was 46% African American, 35% Caucasian, and 19% other races; 9% had previously been pregnant. Positive correlations were observed between lumbar spine BMD and chronological age (r = .301, p < .0001), gynecologic age (r = .349, p < .0001), and BMI (r = .371, p < .0001). Total hip and femoral neck BMD values were significantly higher (p < .05 and p < .05, respectively) in African American participants compared with non-African American participants. Previous history of pregnancy was significantly associated with a lower BMD at the lumbar spine (p < .0001) and the total hip (p < .01) when compared with the BMD of adolescents who had never been pregnant. Cigarette smoking and alcohol use were not associated with significant differences in BMD. Negative correlations were observed between gynecologic age and the levels of BAP (r = -.564, p < .0001), osteocalcin (r = -.349, p < .0001), and uNTX (r = -.281, p < .0001), and between lumbar spine BMD and BAP (r = -.363, p < .0001), osteocalcin (r = -.129, p < .05), and uNTX (r = -.202, p < .001) levels., Conclusions: Our data demonstrate that chronological age, gynecologic age, race/ethnicity, BMI, and previous history of pregnancy are markedly associated with BMD in postmenarchal adolescent girls. Bone accretion in the postmenarchal years continues in the face of a slowdown in bone turnover during this time period.

Background: This observational study aimed to examine the prevalence of activities of daily living, as well as the impact of leisure time activities, on bone mineral density in urban adolescent girls., Methods: Patients completed a 23-item physical activity questionnaire at baseline, recording time spent in various activities in the previous 7 days. In addition to leisure time activities, activities of daily life were also considered. Activities were characterized and scored by metabolic intensity (METPA) and mechanical strain on bone (MECHPA). The METPA score for each activity is the product of the metabolic intensity of the activity and the time spent in the activity. The MECHPA score estimates the mechanical strain on bone from ground reaction forces. The logged scores were divided into quartiles with the lowest quartile as the reference group., Results: Four hundred fifty-five females (ages 12-18 years) completed the survey (62% black and 38% non-black). The log of the overall METPA score was a significant predictor of bone mineral density (i.e. higher METPA score predicted a higher bone mineral density, P = 0.03). A MECHPA score in the highest quartile was associated with a higher bone mineral density (P < 0.05) when compared to the other MECHPA quartiles., Conclusions: In this population of urban adolescent girls, activities of daily living were reported with a higher frequency than sports activities. Results indicated a positive association between the time spent in metabolically intense activities and bone mineral density. There also appears to be a threshold effect for the relationship between activities with the highest mechanical strain and bone mineral density.

Objective: The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception., Study Design: One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment., Results: Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus -1.8% in the placebo group ( P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus -5.1% in the placebo group ( P <.001)., Conclusion: Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.

Study Objective: To examine the relationship between biochemical markers of bone metabolism and hormonal contraception in adolescents., Design: A prospective, observational design., Setting: The study was conducted in four adolescent health clinics in a large metropolitan area., Participants: The study population comprised healthy, postmenarcheal adolescent girls aged 12-18 initiating either medroxyprogesterone acetate (n=53) or an oral contraceptive (OC) containing 20 mug ethinyl estradiol/100 mug levonorgestrel (n=165) and those using no hormonal contraception (n=152)., Interventions: None., Main Outcome Measures: Serum bone specific alkaline phosphatase (BSAP), urinary deoxypyridinoline (DPD), and bone mineral density (BMD) at baseline and 12 months., Results: At 12 month follow-up, serum BSAP levels were significantly higher (P < 0.05) in the control group (40.4 U/L +/- 1.03 SE), than in the DMPA group (35.2 U/L +/- 1.05 SE) and the OC group (35.5 U/L +/- 1.03 SE). There was a trend in urinary DPD levels to be higher (P=0.08) in the control group (9.9 nmol/mmol Cr +/- 1.03 SE) than in the DMPA group (9.1 +/- 1.05 SE) and the OC group (8.9 +/- 1.03 SE). No relationship was found between the biochemical markers and BMD at the lumbar spine or the femoral neck., Conclusions: Over 12 months, there was evidence of increased bone formation and resorption in the control group when compared to that in the DMPA and OC groups. This finding may indicate a suppression of bone metabolism in girls using DMPA or an OC containing 20 mug ethinyl estradiol/100 mug levonorgestrel.

Purpose: To conduct a longitudinal comparison of bone mineral density (BMD) in 370 adolescent girls, aged 12-18, who self-selected depot medroxyprogesterone acetate (DMPA) or an oral contraceptive (OC) containing 20 microg ethinyl estradiol/100 microg levonorgestrel with that in girls who received no hormonal treatment (control group)., Methods: Lumbar spine and femoral neck BMD measurements were obtained by dual energy x-ray absorptiometry at baseline and 12 months. Data were analyzed with repeated measures analysis of covariance methods., Results: Over 12 months, lumbar spine BMD decreased in the DMPA group (n = 29), with a mean percent change of -1.4% (95% confidence interval [CI] -2.73, -0.10), and increased by a mean of 3.8% (95% CI 3.11, 4.57) in the control group [n = 107 (p < .001)]. The increase in mean percent change in lumbar spine BMD in the OC group (n = 79), 2.3% (95% CI 1.49, 3.18), was significantly smaller than in the control group (p = .03). Over 12 months, the mean percent change in femoral neck BMD was -2.2% (95% CI -3.95, -0.39) in the DMPA group, but increased 2.3% (95% CI 1.29, 3.27) in the control group (p < .001). The increase in mean percent change at the femoral neck in the OC group, 0.3% (95% CI -0.87, 1.41), was significantly lower than in the control group (p = .03)., Conclusions: Our study contributes to an increasing body of knowledge indicating a negative impact of DMPA on bone health in young women. Additional findings suggest a potential adverse effect of an OC containing 20 microg ethinyl estradiol/100 microg levonorgestrel on bone health in adolescents.