Dual-energy X-ray absorptiometry diagnostic discordance between Z-scores and T-scores in young adults.

Diagnostic criteria for postmenopausal osteoporosis using central dual-energy X-ray absorptiometry (DXA) T-scores have been widely accepted. The validity of these criteria for other populations, including premenopausal women and young men, has not been established. The International Society for Clinical Densitometry (ISCD) recommends using DXA Z-scores, not T-scores, for diagnosis in premenopausal women and men aged 20-49 yr, though studies supporting this position have not been published. We examined diagnostic agreement between DXA-generated T-scores and Z-scores in a cohort of men and women aged 20-49 yr, using 1994 World Health Organization and 2005 ISCD DXA criteria. Four thousand two hundred and seventy-five unique subjects were available for analysis. The agreement between DXA T-scores and Z-scores was moderate (Cohen's kappa: 0.53-0.75). The use of Z-scores resulted in significantly fewer (McNemar's p<0.001) subjects diagnosed with "osteopenia," "low bone mass for age," or "osteoporosis." Thirty-nine percent of Hologic (Hologic, Inc., Bedford, MA) subjects and 30% of Lunar (GE Lunar, GE Madison, WI) subjects diagnosed with "osteoporosis" by T-score were reclassified as either "normal" or "osteopenia" when their Z-score was used. Substitution of DXA Z-scores for T-scores results in significant diagnostic disagreement and significantly fewer persons being diagnosed with low bone mineral density.

Menstrual cycle and bone health in adolescents.

The intriguing notion of the menstrual cycle's having an acute impact on bone metabolism is examined as an expression of estrogen changes manifest as fluctuations in calcium-regulating hormones or biomarkers of bone formation/resorption. The effects of estrogen, progesterone, androgens, and follicle-stimulating hormones on bone health are also reviewed here. To date, the balance of evidence suggests that the menstrual cycle may exert a significant effect on bone metabolism. Further research needs to be conducted, however, to define these hormonal relationships.

DXA-generated Z-scores and T-scores may differ substantially and significantly in young adults.

Central dual-energy X-ray absorptiometry (DXA) is the gold standard for non-invasive measurement of bone mineral density (BMD). Using this value and subject demographics, DXA software calculates T-scores and Z-scores. Professional society guidelines for the management of osteoporosis are based on T-scores and Z-scores, rather than on the actual BMD value. Although one expects T-scores and Z-scores to be very similar in young men and women for any given BMD measurement, little literature exists on this issue. Our clinical experience shows that some younger adult individuals (premenopausal women and men younger than 50 yr) have larger than expected difference between their DXA T-score and Z-score. This cross-sectional study evaluates the extent of this discordance between Z-scores and T-scores in a sample of 4275 men and women aged 20-49 yr. All subjects were scanned by central DXA using equipment manufactured by GE Lunar, GE, Madison, WI, or Hologic, Inc., Bedford, MA. Significant differences between Z-scores and T-scores were seen within individuals at the lumbar spine, total hip, femoral neck, and trochanter (p value<0.001) for both DXA systems. Although these differences were less than half a standard deviation (SD) in most instances, the magnitude of difference was substantial at times, being 1 or more SD in up to 11% of cases (range: -1.95 to +1.54 SD). The smallest differences were seen at the total hip and the largest differences were seen at the femoral neck for both technologies. This is in part because there is no single standard Z-score definition, resulting in different methods of calculation across, and even within, DXA manufacturers. Standardization of Z-score definition and method of calculation is indicated. DXA Z-scores should be interpreted with caution in men and women aged 20-50 yr.

Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method.

OBJECTIVE: To examine weight changes in a large cohort of obese and nonobese adolescent girls initiating depot medroxyprogesterone acetate (DMPA), an oral contraceptive (OC), or no hormonal contraceptive method (control). DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 450 adolescent girls, aged 12 to 18 years, who attended 4 urban health clinics and selected DMPA, OC, or control. Data collection occurred at baseline and at 6, 12, and 18 months; consisted of structured interview and measurement of height and weight; and occurred from April 19, 2000, through September 26, 2003. MAIN OUTCOME MEASURE: Weight was examined as mean change over 18 months and actual weight at each study visit. On the basis of preliminary analyses, we stratified the sample according to baseline obesity status (nonobese, body mass index [calculated as weight in kilograms divided by the square of height in meters] < 30; obese, body mass index > or =30). RESULTS: Adolescent girls who were obese at initiation of DMPA gained significantly more weight than did obese girls starting OC or control (P<.001 for both). At 18 months, mean weight gain was 9.4, 0.2, and 3.1 kg for obese girls receiving DMPA, receiving OC, and control, respectively. Weight gain in obese girls receiving DMPA was also greater than weight gain in all nonobese categories (4.0 kg, DMPA; 2.8 kg, OC; 3.5 kg, control; P<.001). A significant interaction (P = .006) between length of time receiving DMPA and weight gain was evident for obese subjects. CONCLUSIONS: Over 18 months, DMPA use was associated with increasing rates of weight gain in obese subjects. The potential contribution to severe obesity in this population is concerning.

Depot medroxyprogesterone acetate: implications for weight status and bone mineral density in the adolescent female.

Depot medroxyprogesterone acetate (DMPA) is an effective and easy-to-use contraceptive method for adolescents. However, recent literature suggests that overweight teens may be at increased risk for weight gain while on this contraceptive method, and decreases in bone mineral density have been documented in adolescents on DMPA, particularly with longer duration of use. Consideration of this new literature on DMPA and its implications for clinical practice must be done in the context of the United States having the highest adolescent pregnancy rate in the industrialized world. Hence, potential DMPA risks need to be weighed against the risk of unintended pregnancy in an adolescent.

Bone biochemical markers in adolescent girls using either depot medroxyprogesterone acetate or an oral contraceptive.

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.

Relationship between weight and bone mineral density in adolescents on hormonal contraception.

STUDY OBJECTIVE: Since bone loss has been observed among adolescents on depot medroxyprogesterone acetate (DMPA), a clinical population that commonly experiences weight gain, we were interested in examining the direct relationship between body weight and bone mineral density (BMD) in adolescents on DMPA as compared to those on oral contraceptive pills (OC) or on no hormonal contraception (control). DESIGN: Prospective, Longitudinal study. SETTING: Four urban adolescent health clinics in a large metropolitan area. PARTICIPANTS: Postmenarcheal girls, age 12-18 years, selecting DMPA, OC or no hormonal contraception. INTERVENTIONS: At baseline, 6, 12, 18, and 24 months, all study participants underwent measurement of weight and BMD of the hip and spine. MAIN OUTCOME MEASURES: The correlation between weight and BMD, and the correlation between change in weight and change in BMD were assessed at each time point. RESULTS: Body weight was significantly (P < 0.05) positively correlated with femoral neck BMD and spine BMD at each time point regardless of contraceptive method. Change in body weight at 12 and 24 months was highly correlated with change in femoral neck BMD (P < 0.0001) for all treatment groups. No statistically significant correlation between change in weight and change in spine BMD was seen in the DMPA, OC, or control subjects at 12 or 24 months. CONCLUSION: Weight gain on DMPA may mitigate loss of BMD among adolescent users.

Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants.

STUDY OBJECTIVE: The aim of this study was to measure the prevalence of premature thelarche in infant and toddler girls and to determine if environmental sources of estrogen were associated with early breast development. DESIGN: Observational with mixed methods: Retrospective chart review, cross-sectional component involving an interview survey, along with longitudinal follow-up of girls with thelarche up to six months. SETTING: A general pediatric clinic within a teaching hospital located in a large Midwestern city. PARTICIPANTS: Girls, between the ages of 12 and 48 months, and their mothers, presenting for well-child care. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prevalence of premature thelarche; association of premature thelarche with selected environmental exposures. RESULTS: Among the 318 subjects, the overall prevalence of premature thelarche was measured at 4.7% (n = 15). The prevalence by race/ethnicity was 4.2% among White Non-Hispanics, 4.6% among Blacks and 6.5% among White Hispanics. The peak prevalence occurred between 12-17 months of age. All thelarche cases were Tanner stage 2. No statistically significant relationship was found between premature thelarche and environmental exposures. Upon follow-up, 44% of the cases of premature thelarche had persistent breast development. CONCLUSIONS: Our study demonstrated a higher prevalence of premature thelarche than has been previously reported. This study lacked power because of the small number of premature thelarche cases, the ubiquitous presence of environmental exposure as well as the potentially small effect of each environmental factor. Future studies need to employ a very large sample in order to accurately analyze the relationship between environmental toxicants and premature thelarche.

Association between bone turnover, micronutrient intake, and blood lead levels in pre- and postmenopausal women, NHANES 1999-2002.

BACKGROUND: Blood lead levels (BLLs) have been shown to increase during periods of high bone turnover such as pregnancy and menopause. OBJECTIVES: We examined the associations between bone turnover and micronutrient intake with BLLs in women 20-85 years of age (n = 2,671) participating in the National Health and Nutrition Examination Survey, 1999-2002. METHODS: Serum bone-specific alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides (NTx) were measured as markers of bone formation and resorption, respectively. Lead was quantified in whole blood. The association between tertiles of BAP and NTx, and BLLs was examined using linear regression with natural log transformed BLLs as the dependent variable and interpreted as the percent difference in geometric mean BLLs. RESULTS: In adjusted analyses, mean BLLs among postmenopausal women in the upper tertiles of NTx and BAP were 34% [95% confidence interval (CI), 23%-45%] and 30% (95% CI, 17%-43%) higher than BLLs among women in the lowest tertiles of NTx and BAP, respectively. These associations were weaker, but remained statistically significant, among premenopausal women (NTx: 10%; 95% CI, 0.60%-19%; BAP: 14%; 95% CI, 6%-22%). Within tertiles of NTx and BAP, calcium intake above the Dietary Reference Intake (DRI), compared with below the DRI, was associated with lower mean BLLs among postmenopausal women but not premenopausal women, although most of the associations were not statistically significant. We observed similar associations for vitamin D supplement use. CONCLUSIONS: Bone resorption and bone formation were associated with a significant increase in BLLs among pre- and postmenopausal women.

A longitudinal comparison of body composition changes in adolescent girls receiving hormonal contraception.

The objective of this study was to examine body composition changes in adolescent girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives, or no hormonal contraceptive method. At 6 months, DMPA resulted in significant increases in adiposity with concomitant decreases in lean body mass. Supplemental estrogen may lessen these DMPA effects.

Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study.

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.

Depot medroxyprogesterone acetate and bone mineral density in adolescents--the Black Box Warning: a Position Paper of the Society for Adolescent Medicine.

The purpose of this Position Paper is to review the published Black Box Warning regarding depot medroxyprogesterone acetate (DMPA) and bone loss as it relates to adolescent girls. The scientific findings that prompted the Food and Drug Administration to issue the warning are reviewed and the following additional issues are considered: (1) likely low risk of fracture related to DMPA use, (2) evidence of at least partial recovery after discontinuation of the method, and (3) the need to balance the physical, social and economic cost of adolescent pregnancy versus the immediate and long-term impact of DMPA on bone. A list of clinical guidelines is included, the main recommendation of which is to continue prescription of DMPA, with counseling about the risks and benefits, in most of the adolescent population desiring to use this contraceptive method.

Vitamin D deficiency in adolescent females.

PURPOSE: The purpose of this study was to estimate the incidence of low serum 25-hydroxyvitamin D [25(OH)D] levels in adolescent girls and across racial groups and seasons. METHODS: Healthy postmenarcheal girls (12-18 years of age) were recruited for the study. Serum samples were assayed for 25(OH)D with a competitive protein binding assay (CPB) (Nichols Institute, San Clemente, California). RESULTS: The study included 370 girls (mean age, 15.5 +/- 1.6 y), with a mean serum 25(OH)D level of 53.7(29.0) nmol/L. Seventeen percent of the girls were found to be vitamin D deficient (serum 25(OH)D

The impact of adolescent spirituality on depressive symptoms and health risk behaviors.

PURPOSE: The purpose of this study was to examine spirituality as a meaningful construct in adolescents' lives, and to examine the contribution of spirituality above and beyond that of religiosity to depressive symptoms and health-risk behaviors. METHOD: A total of 134 adolescents from a suburban high school completed a questionnaire assessing spirituality, religiosity, depressive symptoms, and health-risk behaviors. Spirituality was measured with 2 subscales: (1) religious well-being ("I believe that God loves/cares about me") and (2) existential well-being ("Life doesn't have much meaning"). Religiosity was assessed via belief in God/Higher Power and importance of religion. The Children's Depression Inventory-Short Form and the Youth Risk Behavior Survey (YRBS) were used to assess depressive symptoms and health-risk behaviors. RESULTS: The majority of the sample was Caucasian, with a mean age of 16.2 years. Eighty-nine percent reported a belief in God/Higher Power and 77% stated that religion was important in their lives. After controlling for demographics and religiosity, existential well-being and religious well-being accounted for an additional 29% of the variability in depressive symptoms and 17% of the variability in risk behaviors. Existential well-being was the only predictor significant in both final models (p < .01). CONCLUSIONS: Most of these adolescents reported some connection with religious and spiritual concepts, and those with higher levels of spiritual well-being, in particular, existential well-being, had fewer depressive symptoms and fewer risk-taking behaviors. This supports the inclusion of these concepts in our efforts to help promote resilience and healthy adolescent development, and in expanding our investigations beyond religious identification or attendance at religious services to broader concepts of spirituality.

Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception.

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.

Bone mineral density in adolescent and young adult women on injectable or oral contraception.

PURPOSE OF REVIEW: This report critically reviews recent original research articles that pertain to bone mineral density in young adult women utilizing injectable depot medroxyprogesterone acetate or oral contraceptives. RECENT FINDINGS: Some evidence indicates that depot medroxyprogesterone acetate and ultra-low dose oral contraceptives (containing 20 microg ethinyl estradiol) may interfere with the large increases normally observed in adolescence; however, the same degree of bone loss (or lack of bone gain) associated with these drugs is not so impressive in young adult women who would typically be experiencing small changes in bone mass. Data obtained from young adult women show that low dose (30-40 microg ethinyl estradiol) oral contraceptives seem to be more protective of bone than ultra-low dose oral contraceptives. The few extant data suggest that there may be substantial increases in bone mass after discontinuation of depot medroxyprogesterone acetate; no information is available regarding the response of bone after discontinuation of oral contraceptives. As the clinical risk for fracture is usually several decades later, several exogenous factors such as diet and exercise may exert overriding influences on later bone health. Moreover, without contraception, the clinical outcome may be unwanted pregnancy and its potential impact on bone health. SUMMARY: Recent findings suggest that depot medroxyprogesterone acetate and ultra-low dose oral contraceptives may interfere with achieving optimal peak bone mass in very young women; however, there may be substantial recovery after cessation of these methods and overriding long-term influences on bone health imposed by a myriad of lifestyle factors.

Reference values for bone mineral density in 12- to 18-year-old girls categorized by weight, race, and age.

BACKGROUND: Normative bone mineral density (BMD) values for adults do not apply to the pediatric population because of dramatic and variable rates of bone mineral acquisition that take place throughout adolescence. OBJECTIVE: This study was designed to provide normative BMD values for the lumbar spine and femoral neck by age, weight, and race in female adolescents for use by clinicians. MATERIALS AND METHODS: The study population comprised 422 healthy adolescent girls aged 12-18 years recruited from four primary-care clinics. BMD measurements were performed with dual-energy X-ray absorptiometry (DEXA). RESULTS: The major statistical predictors of lumbar spine BMD and femoral neck BMD were race, chronological age, and weight. There was an increase in both lumbar spine and femoral neck BMD that paralleled an increase in age and weight. In addition, the lumbar spine BMD and the femoral neck BMD were higher in the black participants than in the non-black participants with mean BMD values in grams per centimeter squared of 1.02 and 0.98, respectively, for blacks and 0.96 and 0.89, respectively, for non-blacks ( P<0.001). CONCLUSION: Our study produced the largest set of lumbar spine and femoral neck BMD normative values for female adolescents and confirms the importance of both demographic and anthropomorphic variables in determining normative BMD values.

Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls.

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.