Bone Mass Accrual Research Articles

Oral contraceptive use and bone density in adolescent and young adult women

Background Most of the millions of oral contraceptive (OC) users are under 30 years of age and in the critical period for bone mass accrual. Study Design This cross-sectional study of 606 women aged 14–30 years examined both OC duration and estrogen dose and their association with bone mineral density (BMD) at the hip, spine, and whole body (dual-energy X-ray absorptiometry). Results Of 389 OC users and 217 nonusers enrolled, 50% were adolescents (14–18 years). Of OC users, 38% used “low-dose” OCs [<30 mcg ethinyl estradiol (EE)]. In adolescents, mean BMD differed by neither OC duration nor EE dose. However, 19- to 30-year-old women's mean BMD was lower with longer OC use for spine and whole body (p=.004 and p=.02, respectively) and lowest for >12 months of low-dose OCs for the hip, spine and whole body (p=.02, .003 and .002, respectively). Conclusions Prolonged use of today's OCs, particularly <30 mcg EE, may adversely impact young adult women's bone density while using these agents.

Higher Milk Requirements for Bone Mineral Accrual in Adolescent Girls Bearing Specific Caucasian Genotypes in the VDR Promoter

Low milk intakes hamper bone mineral acquisition during adolescence, especially in European girls. We hypothesized that ethnic-specific polymorphisms of the vitamin D receptor gene promoter (VDRp) influence this milk/bone association. We evaluated lumbar spine BMC and BMD, milk/dairy products and calcium intakes, markers of P-Ca metabolism, and VDRp polymorphisms at the Cdx-2 binding (rs11568820) and -1012 (rs4516035) loci in 117 healthy European peri- and postmenarcheal girls (14.9 +/- 1.6 yr) during a 4-yr follow-up. Calcium intakes from milk, nonmilk dairy products, and nondairy products averaged 199, 243, and 443 mg/d at the initiation of the study. Results show no association between milk intakes and bone mass accrual in girls bearing an A/A genotype at the -1012 VDRp locus (30% of the cohort). In contrast, A/G or G/G girls had lower spine BMC (-13%, p = 0.031), BMD (-10%, p = 0.004), and BMD Z-score (-0.84 SD, p = 0.0003) when their milk intakes were <260 ml/d compared with genotype-matched girls with higher milk intakes and with girls with an A/A genotype. The negative impact of low milk intake persisted up to 19.0 +/- 1.7 yr. These findings suggest that European girls bearing a -1012 A/G or G/G VDRp genotype should have higher milk/calcium intakes for optimal vertebral mass accrual during adolescence than girls bearing an A/A genotype, a genotype found in 30% of European and 98% of Asian and Sub-Saharan African populations. VDRp genotype diversity may contribute to the ethnic differences observed in milk requirements for bone health during adolescence.

Bone mineral density and body composition in male children with hypogonadism

Estrogen deficiency in females and androgen deficiency in males may harm periosteal and endosteal apposition, reduce bone size and both cortical and trabecular thickness, modifying in this way the bone structure later in life. To date, few systematic studies on bone mineral density (BMD) and hypogonadism in adolescents are available. Therefore we aimed to determine if sexual hormone deficiency during pubertal age might have an impact on peak bone mass and body composition. We compared areal BMD (L-aBMD), volumetric lumbar spine BMD (L-vBMD), lumbar spine Z-score (L-Z-score), lumbar spine bone mineral content (L-BMC), whole body (wbBMD), normalized whole body (n-wbBMD) BMD, and whole body BMC (wb-BMC) of 25 male children with hypogonadism (HYPO) with 37 sex-, age-, and body mass index-matched healthy subjects (CNT) using dual-energy X-ray absorptiometry. Furthermore we analyzed whether a difference in lean (lean%) and fat (fat%) mass as percentage of body weight and as a lean/fat ratio is present in the two groups of children. HYPO demonstrated a statistically lower L-aBMD, LvBMD, L-BMC, Z score, wbBMD, n-wbBMD, and wb-BMC compared to CNT. CNT showed a higher lean% and lower fat% and a higher lean/fat ratio when compared with HYPO group. Lean mass correlated positively with L-aBMD, L-BMC, and wb-BMC. Our study seems to confirm previous observations that sex hormone deficiency during puberty reduces bone mass accrual. Body composition alterations may play a role in bone parameters during development in healthy as such as in hypogonadal children during developmental age.

Endocrine and musculoskeletal abnormalities in patients with Down syndrome

Down syndrome has a prevalence of one in 500 to one in 1,000 live births and is the most common cause of mental retardation. Most patients are treated in childhood and adolescence for mental or growth retardation. Studies that evaluate bone mass in Down syndrome are limited, and many are small case series in pediatric and adult populations who live either in the community or in residential institutions. Several environmental and hormonal factors contribute to low bone mineral density in such patients. Muscle hypotonia, low amounts of physical activity, poor calcium and vitamin D intakes, hypogonadism, growth retardation and thyroid dysfunction contribute to substantial impairments in skeletal maturation and bone-mass accrual that predispose these patients to fragility fractures. Here, we review indications and limitations of bone-mass measurements in children, summarize the endocrine and skeletal abnormalities in patients presenting with Down syndrome, and review studies that investigate therapeutic strategies for such patients.

Glucocorticoid induced osteoporosis in childhood: prophylaxis and treatment

Bone turnover rate during growth is extremely rapid. Bone growth is under the control of various hormonal environments. Long term administration of glucocorticoid in childhood induced not only osteoporosis but also growth failure via direct action on bone and cartilage and indirectly via hormonal derangements. Sex steroid is one of the important hormones for the bone mineral accrual and for cartilage maturation. Thus glucocorticoid usage during puberty resulted in irreversible effect on bone health including bone growth and peak bone mass accrual. Recently bisphosphonates have been widely used in prophylaxis and treatment of the steroid induced osteoporosis in adult with large amount of evidences, which is largely unknown for the pediatric patients.

Nutrient intakes related to osteoporotic fractures in men and women--the Brazilian Osteoporosis Study (BRAZOS).

BackgroundAdequate nutrition plays an important role in bone mass accrual and maintenance and has been demonstrated as a significant tool for the prevention of fractures in individuals with osteoporosis.ObjectiveThe aim of the present study was to evaluate bone health-related nutrients intake and its association with osteoporotic fractures in a representative sample of 2344 individuals aged 40 years or older in Brazil.MethodsIn a transversal population-based study, a total of 2420 individuals over 40 years old were evaluated from March to April 2006. Participants were men and women from all socio-economic classes and education levels living around the Brazilian territory Individuals responded a questionnaire including self reported fractures as well a 24-hour food recall. Nutrient intakes were evaluated by Nutrition Data System for Research software (NDSR, University of Minnesota, 2007). Low trauma fracture was defined as that resulting of a fall from standing height or less. Nutrient intakes adequacies were performed by using the DRI's proposed values. Statistical analysis comprises Oneway ANCOVA adjusted by age and use of nutritional supplements and multiple logistic regression. SAS software was used for statistical analysis.ResultsFractures was reported by 13% of men and 15% of women. Women with fractures presented significantly higher calcium, phosphorus and magnesium intakes. However, in all regions and socio-economical levels mean intakes of bone related nutrients were below the recommended levels. It was demonstrated that for every 100 mg/phosphorus increase the risk of fractures by 9% (OR 1.09; IC95% 1.05–1.13, p < 0.001).ConclusionThe results demonstrated inadequacies in bone related nutrients in our population as well that an increase in phosphorus intake is related to bone fractures.

Risk Factors and Assessment of Low Bone Mass in the Young Adult Female

Although low bone mass and accelerated bone loss can occur early in life, osteoporosis is usually considered a disorder of postmenopausal women. However, some premenopausal women are also at risk for osteoporosis. Because of a lack of knowledge and few practice recommendations for premenopausal women, it can be more difficult to determine the potential risk and to manage the low bone mass in these women. Low bone density in the young adult female may refl ect attainment of a lower peak bone mass or be secondary to progressive bone loss following attainment of peak bone density. Early bone health is a key determinant of future osteoporosis, optimizing the bone gain by young adulthood and minimizing the bone loss by menopause is the important preventive strategies. Low bone mass in the young adult female may be associated with prolonged amenorrhea, anorexia nervosa, chronic glucocorticoid therapy and diseases that affect calcium and vitamin D metabolism. Also, bone loss may be associated with common conditions such as smoking, dieting, low calcium intake, and low physical activity. This review addresses peak bone mass accrual, risk factors, screening or evaluation and management of low bone mass in young adult female.

Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo

The leptin regulation of bone remodeling, which has been documented through studies of loss-of-function mutations of this hormone or of its receptor in mice and humans, still raised several unanswered questions. For instance, it has been assumed but not formally demonstrated that this regulation occurs through neuronal means. Likewise, it has not been possible until now to dissociate the influence leptin exerts on appetite and energy expenditure from this function. We show here through mouse genetic studies that a deletion of the leptin receptor in neurons results in an increase in bone formation and bone resorption, resulting in a high bone mass as seen in leptin-deficient mice. In contrast, the same deletion in osteoblasts only does not influence bone remodeling. Furthermore, through the use of l/l mice, a model of gain of function in leptin signaling harboring a Y985L substitution in the leptin receptor, we show that leptin signaling inhibits bone mass accrual by up-regulating sympathetic activity independently of any change in appetite or energy expenditure. This work establishes that in vivo leptin regulates bone mass accrual by acting through neuronal means and provides a direct demonstration that this function of leptin can occur independently of its regulation of energy metabolism.

Recovery of muscle atrophy and bone loss from 90 days bed rest: Results from a one-year follow-up

Earlier studies found the recovery of bone loss after clinical immobilization to be incomplete. It has been argued that this is due to the human skeleton's inability to accrue bone mass once peak bone mass has been attained. However, recent studies suggest that bone losses can fully recover when complete functional rehabilitation is achieved. Accordingly, we hypothesized that bone losses by experimental bed rest would recover within one-year of follow-up. Twenty-five men (mean age 32 years, SD 4.2) were randomly assigned to either bed rest only (Ctrl), resistive flywheel exercise (FW), or to a group receiving 60 mg. i.v pamidronate prior to bed rest (Pam). Calf muscle cross sectional area and bone mineral content of the tibia was measured by peripheral quantitative computed tomography. Calcium, PTH and alkaline phosphatase blood levels were assessed along with urinary desoxypyridinoline excretion. Physical activity was assessed by the Freiburg questionnaire. In Pam and FW, diaphyseal bone losses were completely recovered at a 180-day follow-up, and there was even a small surplus after 1 year ( p = 0.016). Epiphyseal bone losses were largely, although not completely recovered after 1 year, when they still amounted to − 0.6% (SD 1.3%, p = 0.034, averaged over all groups). Bone formation and resorption markers had returned to baseline values at this time. However, epiphyseal recovery may still have been on-going, and fitting an exponential model yielded full recovery of the epiphysis within 2 years. Importantly, recovery of calf muscle cross-section and resumption of impact sport activities seemed to precede bone recovery, and bone accrual was closely matching the prior losses on an individual basis. No relationship was found between the epiphyseal BMC deficit at one-year follow-up and the participants' age. Results demonstrate recovery of bed rest induced bone losses in healthy adults. The initial re-accrual rate was remarkably high and is comparable to the accrual of bone mass during the pubertal growth spurt. This and the fact that the recovery of bone appeared to be tightly regulated, and generally followed neuromuscular recovery underline the adult skeleton's capability to adapt to mechanical stimuli.

Calcium and vitamin D and bone strength ‐ Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 ‐ Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies

Calcium and vitamin D and bone strength ‐ Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 ‐ Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies

Percent true calcium absorption, mineral metabolism, and bone mass in children with arthritis: Effect of supplementation with vitamin D3 and calcium

To assess whether percent true calcium absorption (alpha) is normal and whether supplementation with placebo, vitamin D3 (2,000 IU/day), calcium (1,000 mg/day), or vitamin D3 plus calcium improves alpha, mineral metabolism, or bone mass accrual in children with arthritis. Eighteen children received all 4 treatments, each for 6 months, in 4 different, randomly assigned orders. Changes in levels of 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D), parathyroid hormone, bone turnover markers, and minerals and in bone mineral content were measured. Calcium absorption was determined with a dual stable isotope method using 48Ca administered intravenously and 46Ca administered orally, and measuring 48Ca, 46Ca, and 42Ca in a 24-hour urine specimen by high-resolution inductively coupled plasma mass spectroscopy. Wilcoxon's signed rank test was used both to identify significant change over the treatment period with a given regimen and to compare change with an experimental treatment versus change with placebo. Percent true calcium absorption was in the lower-normal range and did not differ by treatment (mean+/-SD 28.3+/-20.2% with placebo, 26.1+/-12.1% with calcium, 19.2+/-11.7% with vitamin D3, and 27.1+/-16.5% with vitamin D3 plus calcium). With vitamin D3 and vitamin D3 plus calcium treatment, 25(OH)D levels were increased and 1,25(OH)2D levels were maintained. Serum calcium levels were increased only with vitamin D3 and vitamin D3 plus calcium treatment. Levels of bone turnover markers and increases in bone mineral content did not differ by treatment. The findings of this study indicate that percent true calcium absorption is low-normal in children with arthritis. Vitamin D3 at 2,000 IU/day increases serum 25(OH)D and calcium levels but does not improve bone mass accretion. Calcium at 1,000 mg/day also failed to improve bone mass.

Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls

We assessed the main and interaction effects of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. A total of 228 premenarche Chinese girls (9-11.5 years old) were recruited for a 2-year follow-up study. Bone mineral density (BMD) at the total body, lumbar spine (L1-L4), and total left hip were measured by dual-energy X-ray absorptiometry at baseline and follow-up. The -174G/C and -634C/G polymorphism of IL-6 gene, and PvuII and XbaI polymorphisms of the estrogen receptor (ER)-alpha gene, were determined. The -634C/G polymorphism of the IL-6 gene and PvuII polymorphism of ER-alpha gene were significantly associated with bone mass accrual after adjusting the potential confounding factors. Girls with pp genotype of ER-alpha gene had greater percentage accrual in BMD of total body (P = 0.010) and femoral intertrochanter (P = 0.038) than their PP and Pp counterparts. Girls with CC genotype of IL-6 -634G/C gene had higher percentage accrual in BMD of total body (P = 0.032) and femoral trochanter (P = 0.048) than their CG + GG counterparts. Significant interaction effects of IL-6 -634C/G polymorphism and ER-alpha PvuII polymorphism were observed on percentage change in BMD of total left hip (P = 0.009) and femoral intertrochanter (P = 0.007). The genotype CC (IL-6 -634C/G) x pp (ER-alpha PvuII) was associated with greater BMD accrual than other genotype combination in Chinese adolescent girls. We found that the IL-6 -634C/G and ER-alpha PvuII polymorphism were significantly associated with BMD accrual and that they have an interactional effect on BMD accrual in Chinese adolescent girls.

Percent true calcium absorption, mineral metabolism, and bone mineralization in children with cystic fibrosis: Effect of supplementation with vitamin D and calcium

To assess whether percent true calcium absorption (alpha) is normal in children with cystic fibrosis (CF) and to assess whether supplementation with 2,000 IU vitamin D(3), 1 g calcium, or both will alter alpha, mineral metabolism, and/or bone mass in children with CF. Fifteen children ages 7-13 were randomly assigned to one of four different orders to receive all four 6-month treatments including placebos. Change in 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), PTH, bone turnover markers, and minerals after 6 months, and bone mineral content (Hologic 1000W) after 9 months was measured. alpha was measured by a dual stable isotope method using (48)Ca intravenously and (46)Ca orally and measuring (48)Ca, (46)Ca, and (42)Ca in a 24-hr urine using High Resolution Inductively Coupled Mass Spectroscopy (HR-ICP-MS). Analysis used Wilcoxon Sign Ranks. alpha was in the normal range and did not differ by treatment (P 35 +/- 10%, Ca 38 +/- 23%, D 36 +/- 11%, D + Ca 46 +/- 21%). One gram calcium did not increase serum or urine calcium. Two thousand IU D(3) did not increase 25-OHD or change 1,25(OH)(2)D. Serum and urine minerals, markers of bone turnover and bone mineral gains did not differ by treatment. alpha is normal in children with CF. One gram calcium and/or 2,000 IU D(3) does not change alpha or increase 25-OHD, serum calcium, or mineralization. Longer trials of a significantly higher dose of vitamin D(3) shown to increase serum 25-OHD are needed to assess effects on mineral metabolism and bone mass accrual. However, study of therapeutic options other than calcium and vitamin D should be encouraged.

Skeletal effects of estrogen and mechanical loading are structurally distinct

Estrogen has been suggested to influence skeletal homeostasis by both increasing the sensitivity of the feedback control system for skeletal rigidity and acting directly on bone surfaces. The objective of the present study was to explore the proposed interaction between the skeletal effects of estrogen and locomotion. Thirty 3-week-old littermates of female Sprague–Dawley rats were first randomly assigned into bilateral sham (E +) or ovariectomy (E −) surgery after which, the left hindlimb each study animal was cast immobilized (L −) while the right limb served as locomotively loaded control (L +), a classic 2 × 2 factorial study design. After 8-week study period, femoral neck, femur midshaft and distal metaphysis were analyzed by peripheral quantitative computed tomography (pQCT), microcomputed tomography (µCT), and mechanical testing. The loading-induced effects were virtually identical in the estrogen-replete (E +) and estrogen-deplete (E −) groups (Femoral neck: + 78% vs. + 69% in the tCSA, + 74% vs. + 55% in the tBMC, − 6.0% vs. − 7.2% in the tBMD, and + 33% vs. + 58% in the F max; Femoral midshaft: + 6.9% vs. + 3.9% in the cCSA, + 13% vs. + 13% in the tCSA, + 23% vs. + 16% in the cBMC, + 5.2% vs. + 5.1% in the cBMD, and + 8.0% vs. + 8.0% in the F max, respectively. All comparisons, NS), challenging the alleged modulatory effect of estrogen on skeletal mechanosensitivity. Estrogen did not have an independent effect on the periosteal apposition at any of the evaluated bone regions. Instead, according to its primary reproductive function, the effects of estrogen were restricted to accrual of bone mass only, the stimulus being apparent at the endosteal surface of cortex and trabecular structure of the distal metaphysis. In conclusion, the present results indicate that that the actions of estrogen and loading on bone structure are independent and additive in nature.

Bone Metabolism in Adolescent Boys with Anorexia Nervosa

Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys. We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers. We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12-19 yr old. Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers. AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.

Long‐Term Skeletal Effects of Eating Disorders with Onset in Adolescence

Anorexia nervosa (AN), an eating disorder characterized by severe undernutrition and associated with hypogonadotropic hypogonadism, causes marked deficits in bone mass accrual when the disorder begins in the teenage years. Although bone mass accrual improves with weight gain and menstrual recovery, residual deficits persist. Women with a history of teenage onset of AN are more likely to be osteopenic than age-matched women without this history, even after many years of weight and menstrual recovery. Non-recovered women with persistent low weight and amenorrhea have continued decreases in bone density, with a high prevalence of both osteopenia and osteoporosis. Unlike anorexia nervosa, normal-weight bulimia is not associated with low bone density, unless there is a past history of low weight or amenorrhea. A second possible skeletal effect of teenage-onset anorexia nervosa is short stature. Duration of illness and time of onset of anorexia nervosa in relation to the pubertal growth spurt are likely important determinants of statural growth. Adolescent boys with anorexia nervosa are more likely than adolescent girls to have short stature, possibly because growth potential persists for two years longer in boys than in girls. Thus, many adolescent girls may have completed growth or be close to growth completion at the time that they develop anorexia nervosa, whereas adolescent boys may still have significant growth potential remaining. This remaining growth potential may be impaired as a consequence of low levels of insulin-like growth factor-I (IGF-I) levels from persistent undernutrition.

Bone metabolism in adolescent athletes with amenorrhea, athletes with eumenorrhea, and control subjects.

We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass.

Impaired bone health in anorexia nervosa

Anorexia nervosa (AN), a condition of malnutrition, has a multitude of effects, including low bone mineral density (BMD). Much has been discovered over the last couple of decades regarding the extent and pathophysiology of low BMD in AN, including the role of gonadal steroids, neuroendocrine hormones and appetite-regulating peptides. The effects of AN on bone are particularly concerning in adolescents, who are in the process of accruing peak bone mass, and decreased rates of bone-mass accrual in these critical years are predictive of poor bone health in later life. Although dual-energy x-ray absorptiometry continues to be the standard technique for monitoring BMD, newer techniques such as quantitative computed tomography and calcaneal ultrasound are being explored. Weight and menses recovery continue to be the most effective treatment for improving BMD in AN. Further research is needed to translate the pathophysiology being unraveled into clinical applications for improving BMD in AN.

Bone density in the adolescent athlete

Adolescence is a critical time for bone mass accrual, and increases in bone mass through puberty are dependent on rising levels of gonadal steroids, growth hormone and insulin like growth factor-1. Many high school girls are involved in athletic activities, and as many as 23.5% of adolescent athletes have been reported to develop amenorrhea. This review focuses on (1) factors that determine which athletes are likely to develop amenorrhea, such as a negative energy balance state, low levels of leptin and high levels of ghrelin, and (2) the impact of hypogonadism in athletes on bone metabolism. Beneficial effects of increased mechanical loading from athletic activity do not appear to protect against the deleterious effects of hypogonadism in adolescent athletes.

Interaction of the polymorphism of vitamin D receptor gene start codon with physical activity on bone mass accrual in Chinese adolescent girls

To investigate the association between the polymorphism of vitamin D receptor (VDR) gene start codon (Fok I) and bone mass accrual, and assessing if such an association could be modified by physical activity in Chinese adolescent girls. A total of 228 premenrche Chinese girls (9-11.5-years-old) were recruited for 2-year study. Bone mineral densities (BMD) at the total body, total left hip (including femoral neck, trochanter, intertrochanteric and Ward's triangle area) and lumbar spine (L1-L4) were measured by dual energy X-ray absorptiometry. The Fok I polymorphism of VDR gene was detected with PCR-RFLP. There remained 176 available subjects in our cohort when 2-year study was completed. No significant association was observed between Fok I polymorphism of VDR gene and percentage change in BMD at all sites. Girls with FF genotype had lower percentage change in total left hip BMD (THBMD) and femoral neck BMD (FNBMD) than girls with Ff + ff genotype only in low physical activity(< 1197 kJ/d), and physical activity was associated with percentage change in THBMD and FNBMD only in FF genotype group. The Fok I polymorphism of VDR gene should have significant interaction effect with physical activity on bone mass accrual in Chinese adolescent girls. Girls with FF genotype in low physical activity would be the potential risk population for low bone mass accrual, and high physical activity would be of benefit to gain higher bone mass accrual for girls with FF genotype.