Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera) effects on bone health in adolescents: study design, population characteristics and baseline bone mineral density.

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.

Opioid Use Disorders.

Opioid use and addiction in adolescents and young adults is a health problem of epidemic proportions, with devastating consequences for youth and their families. Opioid overdose is a life-threatening emergency that should be treated with naloxone, and respiratory support if necessary. Overdose should always be an opportunity to initiate addiction treatment. Detoxification is often a necessary, but never sufficient, component of treatment for OUDs. Treatment for OUDs is effective but treatment capacity is alarmingly limited and under-developed. Emerging consensus supports the incorporation of relapse prevention medications such as buprenorphine and extended release naltrexone into comprehensive psychosocial treatment including counseling and family involvement.

Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections.

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.

Biopsychosocial variables associated with substantial bone mineral density loss during the use of depot medroxyprogesterone acetate in adolescents: adolescents who lost 5% or more from baseline vs. those who lost less than 5%.

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.

Bone mineral density in postmenarchal adolescent girls in the United States: associated biopsychosocial variables and bone turnover markers.

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.