Attainment Of Peak Bone Mass Research Articles

Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature

Functional hypothalamic amenorrhea (FHA) impairs the attainment of peak bone mass and as such can increase the risk of fractures later in life. To document available treatment strategies, we conducted a systematic review of the literature. We report that hormonal therapies have limited effectiveness in increasing bone mass, whereas increased caloric intake resulting in weight gain and/or resumption of menses is an essential strategy for restoring bone mass in women with FHA. Women with functional hypothalamic amenorrhea (FHA) may not achieve peak bone mass (PBM), which increases the risk of stress fractures, and may increase the risk of osteoporotic fractures in later life. To identify effective treatment strategies for women with FHA, we conducted a systematic review of the literature. We included randomized controlled trials (RCTs), cross-sectional studies, and case studies that reported on the effects of pharmacological and non-pharmacological interventions on bone mineral density (BMD) or bone turnover in women with FHA. Most published studies (n=26) were designed to treat the hormonal abnormalities observed in women with FHA (such as low estrogen, leptin, insulin-like growth factor-1, and DHEA); however none of these treatments demonstrated consistent improvements in BMD. Therapies containing an estrogen given for 8-24 months resulted in variable improvements (1.0-19.0%) in BMD, but failed to restore bone mass to that of age-matched controls. Three studies reported on the use of bisphosphonates (3-12 months) in anorexic women, which appear to have limited effectiveness to improve BMD compared to nutritional treatments. Another three investigations showed no improvements in BMD after androgen therapy (DHEA and testosterone) in anorexic women. In contrast, reports (n=9) describing an increase in caloric intake that results in weight gain and/or the resumption of menses reported a 1.1-16.9% increase in BMD concomitant with an improvement in bone formation and reduction in bone resorption markers. Our literature review indicates that the most successful, and indeed essential strategy for improving BMD in women with FHA is to increase caloric intake such that body mass is increased and there is a resumption of menses. Further long-term studies to determine the persistence of this effect and to determine the effects of this and other strategies on fracture risk are needed.

Anorexia, bulimia, and the athletic triad: Evaluation and management

Caloric restriction caused by undernutrition or over-exercise is increasingly common and has significant health consequences such as hypothalamic amenorrhea, infertility, attainment of low peak bone mass, and bone loss leading to fracture. In these patients, the pathophysiology of amenorrhea and bone loss is multifactorial, involving hormones that integrate the nutritional state with the hypothalamic-pituitary-ovarian axis, including leptin and possibly ghrelin. The pathophysiology of bone loss includes nutritional deficiencies, possibly estrogen deficiency, and direct and indirect effects of leptin on bone. Identifying patients at risk for low bone mineral density and fracture is important, as is screening with dual energy radiograph absorptiometry. Treatment has focused on oral contraceptive use, yet improved bone mineral density is marked by nutritional recovery and anovulation reversal. Therefore, resolving the nutrition deficiency should be the cornerstone of treatment. Cognitive-behavioral therapy aims for weight recovery, which can lead to reversal of amenorrhea and improvement in other associated metabolic abnormalities. During treatment, estradiol levels can be followed to assess hypothalamic-pituitary-ovarian recovery because estradiol secretion may increase well before ovulation occurs. In patients failing the above interventions, hormone replacement should be considered, but bone mineral density should be followed because patients may continue to lose bone despite treatment with oral contraceptives if nutrition is not improved.

PTHR1 Polymorphisms Influence BMD Variation through Effects on the Growing Skeleton

We investigated whether polymorphisms in PTHR1 are associated with bone mineral density (BMD), to determine whether the association of this gene with BMD was due to effects on attainment of peak bone mass or effects on subsequent bone loss. The PTHR1 gene, including its 14 exons, their exon-intron boundaries, and 1,500 bp of its promoter region, was screened for polymorphisms by denaturing high-performance liquid chromatography (dHPLC) and sequencing in 36 osteoporotic cases. Eleven single-nucleotide polymorphisms (SNPs), one tetranucleotide repeat, and one tetranucleotide deletion were identified. A cohort of 634 families, including 1,236 men (39%) and 1,926 women (61%) ascertained with probands with low BMD (Z< -2.0) and the Children in Focus subset of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (785 unrelated individuals, mean age 118 months), were genotyped for the five most informative SNPs (minor allele frequency >5%) and the tetranucleotide repeat. In our osteoporosis families, association was noted between lumbar spine BMD and alleles of a known functional tetranucleotide repeat (U4) in the PTHR1 promoter region (P = 0.042) and between two and three marker haplotypes of PTHR1 polymorphisms with lumbar spine, femoral neck, and total hip BMD (P = 0.021-0.047). This association was restricted to the youngest tertile of the population (age 16-39 years, P = 0.013-0.048). A similar association was found for the ALSPAC cohort: two marker haplotypes of SNPs A48609T and C52813T were associated with height (P = 0.006) and total body less head BMD (P = 0.02), corrected for age and gender, confirming the family findings. These findings suggest a role for PTHR1 variation in determining peak BMD.

Bone mass status of school-aged children in Taiwan assessed by quantitative ultrasound: the Nutrition and Health Survey in Taiwan Elementary School Children (NAHSIT Children 2001-2002).

Bone health status in childhood and adolescence may be important factors influencing the attainment of peak bone mass. The Nutrition and Health Survey in Taiwan Elementary School Children 2000-2001 was carried out to evaluate the overall nutrition and health status of school children aged between 6 and 13 years. The survey was conducted using a multi-stage complex sampling scheme. Townships and city districts in Taiwan were classified into 13 strata. Bone mass measured as broadband ultrasound attenuation was taken at heel by quantitative ultrasound bone densitometry. A total of 1164 boys and 1016 girls who had complete physical examination data with ultrasound bone scan were included in the current analysis. There were no apparent differences in BUA across all strata for both genders. In both boys and girls, age, height, body weight, BMI, and intake frequencies of vegetables and fruits/juices were significantly related to BUA. Results of multivariate regression showed that age (beta=1.36, p=0.0002) and body weight (beta=0.40, p<0.0001) were significant predictors for BUA in boys, whereas in girls body weight (beta=0.47, p<0.0001), height, (beta=0.20, p=0.01), dietary phosphorus intake (beta=-0.002, p=0.038), and frequency of fruit/juice intake (beta=0.15, p=0.029) remained statistically significant. The differential effects dietary intake variables on BUA in boys and girls may be in part due to the development of puberty. It would be necessary to include levels of physical activity in future analyses for better understanding factors influencing the development of peak bone mass in Taiwanese children.

Milk Supplementation and Bone Health in Young Adult Chinese Women

Milk is potentially beneficial for bone health, particularly for Chinese populations where consumption of dairy products is low. There are few data about milk consumption by Chinese women aged 20-35 years. This study examines whether milk supplement over 2 years caused increased bone mineral density (BMD) in Chinese women aged 20-35 years. Four hundred forty-one community-living women living in Hong Kong SAR (221) and Beijing (220) China were randomized to receive milk supplement or nothing. The supplement consisted of two sachets of milk powder (1000 mg calcium, 80 microg vitamin K(1)), for 24 months. BMD at total hip, total spine, and whole body was measured at baseline and at 6, 12, 18, and 24 months; blood specimens were analyzed at baseline and at 3 and 24 months for biochemical indices of bone turnover and vitamin K. Urine samples also were collected. Analysis was by intention to treat as well as per protocol. Differences in change from baseline between the milk and control groups were analyzed using the mixed models approach to repeated measures, including the baseline value as a covariate. Both groups had an increase in BMD and a decrease in bone turnover markers over time, as an indicator of the process of attainment of peak bone mass during this period. Apart from a higher total spine BMD at 6 months in the milk group using per protocol analysis, there was little significant difference observed between the milk group and the control group. Age-related bone metabolism and lack of compliance most likely explain the lack of consistent changes in BMD or bone biochemical measures in response to milk supplementation for 2 years in Chinese women aged 20-35 years.

Decreased peak bone mass is associated with a 3-bp deletion/insertion of the CYP19 intron 4 polymorphism: Preliminary data from the GOOS study

Finding that estrogen plays an important role in bone homeostasis in men prompted research on relationship of polymorphism at the CYP19 gene and the bone mass. Therefore, influence of 3-bp deletion/insertion polymorphism of CYP19 (TTTA)7 allele on the peak bone mass attainment in males was studied. Fifty-eight unrelated male participants, aged 21-35, were selected depending on the presence of (TTTA)7 (no.=19) or (TTTA)7-3 (no.=39) alleles from the initial cohort of 92 young males. Heterozygotes (TTTA)7/(TTTA)7-3 (no.=13) were not included in the analysis. Serum levels of estradiol, free testosterone, 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, and beta-crosslaps were measured. Bone mass was measured by DXA at the hip and at the spine. (TTTA)7-3 allele was associated with significantly lower femoral neck bone mineral density (BMD) (p=0.02). Logistic regression model indicated strong association of (TTTA)7-3 allele with low BMD in the range of osteopenia/osteoporosis (p=0.014, odds ratio 12.36, confidence intervals 1.65-92.46). In the present study association of 3-bp deletion polymorphism of the (TTTA)7 allele with decreased peak bone mass in males is reported for the first time. However, further studies are necessary to elucidate the functional relevance of this polymorphism.

Contraception

Contraception

B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo

AbstractBone homeostasis is regulated by a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclastogenesis is controlled by the ratio of receptor activator of NF-κB ligand (RANKL) relative to its decoy receptor, osteoprotegerin (OPG). The source of OPG has historically been attributed to osteoblasts (OBs). While activated lymphocytes play established roles in pathological bone destruction, no role for lymphocytes in basal bone homeostasis in vivo has been described. Using immunomagnetic isolation of bone marrow (BM) B cells and B-cell precursor populations and quantitation of their OPG production by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcriptase–polymerase chain reaction (RT-PCR), cells of the B lineage were found to be responsible for 64% of total BM OPG production, with 45% derived from mature B cells. Consistently B-cell knockout (KO) mice were found to be osteoporotic and deficient in BM OPG, phenomena rescued by B-cell reconstitution. Furthermore, T cells, through CD40 ligand (CD40L) to CD40 costimulation, promote OPG production by B cells in vivo. Consequently, T-cell–deficient nude mice, CD40 KO mice, and CD40L KO mice display osteoporosis and diminished BM OPG production. Our data suggest that lymphocytes are essential stabilizers of basal bone turnover and critical regulators of peak bone mass in vivo.

Endogenous TNFα Lowers Maximum Peak Bone Mass and Inhibits Osteoblastic Smad Activation Through NF-κB

Endogenous TNFalpha prevents the attainment of maximum achievable peak bone mass in vivo. In vitro, TNFalpha suppresses BMP-2- and TGFbeta-mediated Smad activation through induction of NF-kappaB. Consistently, pharmacological suppression of NF-kappaB augments osteoblast differentiation and mineralization in vitro. Osteoporosis is a major health threat. Traditional therapeutic strategies have centered on anti-catabolic drugs that block bone resorption. Recently focus has shifted to anabolic agents that actively rebuild lost bone mass. Future strategies may involve elevating peak bone mass to delay osteoporosis development. Recent in vitro studies show that TNFalpha represses osteoblast differentiation and mineralization; however, the mechanisms are poorly understood and the impact of basal TNFalpha concentrations on the acquisition of peak bone mass in vivo is unknown. We examined peak BMD, bone volume, and bone turnover makers in mice deficient in TNFalpha or its receptors. We further examined the effect of TNFalpha on Smad-induced signaling by TGFbeta and BMP-2 in vitro using a Smad responsive reporter. The effect of TNFalpha-induced NF-kappaB signaling on Smad signaling and on in vitro osteoblast mineralization was examined using specific NF-kappaB inhibitors and activators, and effects of TNFalpha-induced NF-kappaB signaling on BMP-2-induced Runx2 mRNA were examined using RT-PCR. Mice null for TNFalpha or its p55 receptor had significantly increased peak bone mass, resulting exclusively from elevated bone formation. In vitro, TNFalpha potently suppressed Smad signaling induced by TGFbeta and BMP-2, downregulated BMP-2-mediated Runx2 expression, and inhibited mineralization of osteoblasts. These effects were mimicked by overexpression of NF-kappaB and prevented by pharmacological NF-kappaB suppression. Our data suggest that TNFalpha and NF-kappaB antagonists may represent novel anabolic agents for the maximization of peak basal bone mass and/or the amelioration of pathological bone loss.

N−3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2Study

Background:Knowledge of the influence of nutritional intake on bone health is limited. Polyunsaturated fatty acids have been suggested to influence bone growth and modeling in humans, although data are sparse.Objective:The objective was to investigate the role of fatty acids in bone accumulation and the attainment of peak bone mass in young men.Design:The cohort studied consisted of 78 healthy young men with a mean age of 16.7 y at baseline. Bone mineral density (BMD; in g/cm2) of total body, hip, and spine was measured at baseline and at 22 and 24 y of age. Fatty acid concentrations were measured in the phospholipid fraction in serum at 22 y of age.Results:Concentrations of n−3 fatty acids were positively associated with total BMD (r= 0.27, P= 0.02) and spine BMD (r= 0.25, P= 0.02) at 22 y of age. A positive correlation between n−3 fatty acid concentrations and the changes in BMD at the spine (r= 0.26, P= 0.02) was found between 16 and 22 y of age. Concentrations of docosahexaenoic acid (DHA, 22:6n−3) were positively associated with total BMD (r= 0.32, P= 0.004) and BMD at the spine (r= 0.30, P= 0.008) at 22 y of age. A positive correlation was also found between DHA concentrations and the changes in BMD at the spine (r= 0.26, P= 0.02) between 16 and 22 y of age.Conclusion:The results showed that n−3 fatty acids, especially DHA, are positively associated with bone mineral accrual and, thus, with peak BMD in young men.

Dietary protein intakes and bone growth

Peak bone mass is a significant determinant of fracture risk later in life. Nutritional intakes, particularly proteins, are able to modulate the genetic potential, with effects starting as early as in utero. There is a positive correlation between yearly lumbar and femoral bone mass gain, and protein intake. Dairy products consumption positively influences bone mineral density at the spine, hip and forearm in adolescents, leading thereby to a higher peak bone mass. Nutritional intakes, particularly proteins, are associated to bone growth, hence to bone strength and resistance to fracture later in life. The growth hormone IGF-I-target organ axis is likely to be implicated in this process. Variations in the protein intake within the “normal” range can have a significant effect on skeletal growth and thereby modulate the genetic potential in peak bone mass attainment.

Osteopenia and cancer in children and adolescents

The attainment of a satisfactory peak bone mass, which is accomplished largely by the end of adolescence, is the best protection against excessive bone mineral loss in late adulthood. Factors that influence this process include age, race, sex, body size, pubertal status, diet, physical activity, and other lifestyle elements. Cancer and its treatment in children and teenagers adversely impact bone mineralization. In particular, chemotherapy (especially glucocorticosteroids and methotrexate) and cranial irradiation (apparently by reducing growth hormone secretion and by causing hypogonadotropic hypogonadism) interfere with normal bone turnover. Resorption often exceeds formation, resulting in net bone mineral loss and providing a rational basis for the use of antiresorptive drugs. Such osteopenia may be symptomatic, with pain and abnormal gait, and increases the risk of fractures several fold. The disorder is compounded by reduced physical activity, so programs to reduce this deficit are of measurable benefit. All of those engaged in the care of children and adolescents with cancer have an opportunity to improve the bone health of these young people and to limit their risk of developing osteoporosis and fragility fractures in adult life.

Peripheral bone mineral density and its predictors in healthy school girls from two different socioeconomic groups in Delhi

Peripheral bone density measurements are scarce and the factors, which predict bone mineral density at these sites, especially in children, are not clearly known. In this study, age, height, weight and alkaline phosphatase had a significant association on peripheral bone mineral density in healthy Indian school girls. Factors that lead to the attainment of peak bone mass at peripheral sites, during period of growth are not clearly known. Six-hundred and sixty-four randomly selected 7- to 17-year-old girls from upper and lower socioeconomic status (USES/LSES) schools were assessed clinically and a recording of their height and weight was undertaken. Serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) were measured in all of them. Bone mineral density (BMD) was measured at the distal forearm (BMDdf) and calcaneum (BMDca) by peripheral dual energy X-ray absorptiometry (pDXA). Girls belonging to the USES were significantly taller (149.7 +/- 12.3 cm vs 144.4 +/- 11.9 cm; P < 0.001) and weighed more (44.3 +/- 12.9 kg vs 35.9 +/- 10.0 kg; P < 0.001) than girls from the LSES. USES girls had a significantly higher mean serum calcium (9.3 +/- 0.7 mg/dl vs 9.2 +/- 0.8 mg/dl; P < 0.05) and significantly lower alkaline phosphatase (316 +/- 166 IU/l vs 423 +/- 228 IU/l; P < 0.01) and iPTH (29.9 +/- 18.4 pg/ml vs 45.7 +/- 64.6 pg/ml; P < 0.01). There was no significant difference in mean serum phosphorus and 25-OHD levels between the two groups. USES subjects had higher BMD at both sites than LSES subjects. BMDdf and BMDca increased with age and tended to plateau by 16 years and 12 years of age respectively in both the groups. Age, height and weight explained approximately 50% of the variability, while biochemical parameters explained approximately 30% of variability in BMD at both the sites. The only biochemical parameter which had a significant association with BMD was ALP at the distal forearm. In conclusion, age, nutrition, height and weight are significantly associated with BMD at peripheral sites.

Efficacy of optimization of vitamin D in preventing osteoporosis and osteoporotic fractures: A systematic review

Increased intake or supplementation of vitamin D is often recommended for normal bone health; however, its preventive effect on osteoporosis has not been fully evaluated. The aim of this review is to gather evidence of the efficacy of the optimization of vitamin D nutrition in preventing osteoporosis and osteoporotic fractures. PubMed was used for searching the relevant literature using the MeSH terms "Bone Density (limited to "human", "female", and "English" literature)" or "Fractures (limited to "human", "age ≥45 years", and "English" literature)", and "Vitamin D". The searches yielded 19 randomized controlled trials (RCTs), nine cohort studies, 19 case-control studies, 19 cross-sectional studies, and one meta-analysis. We attempted to answer three questions: 1) does increased vitamin D intake prevent bone loss in peri- and postmenopausal women?, 2) does increased vitamin D intake prevent osteoporotic fractures in the elderly?, and 3) does increased vitamin D in take positively affect peak bone mass attainment in young women? The answer to questions 1 and 2 is that a vitamin D intake of 10-17.5 μg/day (400-700 IU/day) or more is effective in preventing bone loss in late postmenopausal women and an intake of 17.5-20 μg/day (700-800 IU/day) or more together with a calcium supplement reduces the risk of osteoporotic fractures. For question 3, some lines of evidence support the negative effect of low vitamin D nutrition on the attainment of peak bone mass in young women. Further studies are needed to clarify the effect of vitamin D in this age group.

Bone Mineral Density Assessment in Premenopausal Women

In the absence of fragility fractures, low bone mineral density may reflect attainment of a lower peak bone mass in comparison with the young adult mean value. It is necessary to distinguish between low peak bone mass and a systemic disorder resulting in low bone mineral density and skeletal fragility. Low peak bone mass in the absence of fragility fracture or progressive bone loss may not require pharmacological intervention. However, systemic disorders contributing to bone loss do require diagnosis and intervention. Common causes of low bone density in premenopausal women include ovulatory disturbances and low body weight. Other diseases, conditions or medications may also contribute to bone loss and these should be identified and treated if present. Fracture risk is reduced by lifestyle changes and pharmacological intervention in those with glucocorticoid-induced bone loss. Discontinuing depo medroxyprogesterone acetate use has been associated with improvements in bone mineral density. Bone mineral density alone is insufficient for the diagnosis of osteoporosis in premenopausal women in the absence of fragility fractures. Bone mineral density testing should only be performed in premenopausal women in the presence of approved indications.

Bone mineral density and depot medroxyprogesterone acetate

Introduction Depot medroxyprogesterone acetate (DMPA) suppresses pituitary gonadotrophin output, thus, suppressing ovulation. Estrogen production from the ovary is also strongly inhibited, and the resulting estrogen deficiency has a detrimental impact on bone. Depot medroxyprogesterone acetate may be particularly detrimental in young women, as it may impede attainment of peak bone mass, and switching to a different contraceptive is recommended. However, the effect of sequential use of DMPA with other contraceptives in this age group has not been investigated. Methods This was a cross-sectional analysis of 218 DMPA users who were 20 years or older (mean, 31 years, ±8.9 SD) at the time of bone mineral density (BMD) estimation. The majority of women had used one or more contraceptive beside DMPA. The most commonly used alternative contraceptive was the oral combined pill (OCP). It was used by 65% of women ( n=143) and for an average duration of 6 years. A logistic regression model was used to estimate the association between potential risk factors and low bone mass. Results The prevalence of low bone mass at either hip or spine ( T≤1) was 41%. The prevalence of a T score below −2.5 was 5%, and 45% of women had already sustained one fracture. Younger age was associated with higher BMD [odds ratios (ORs), 0.054; 95% confidence interval (CI), 0.007–0.431]. However, this protective effect of age was lost once the interaction between the duration of both DMPA and OCP was introduced into the model (OR for low BMD, 1.42; 95% CI, 1.09–1.8). The use of DMPA first before ever use of OCP was particularly detrimental to BMD (OR, 3.94; 95% CI, 1.08–14.0). On the contrary, body mass index was positively associated with BMD (OR, 0.86; 95% CI, 0.8–0.9). No other demographic or anamnestic variables significantly predicted the presence of low BMD in this group of young women. This group of DMPA users appear to be at a very high risk of both low BMD and fractures, possibly independently of DMPA use. This needs to be considered when writing guidelines for risk assessment. Conclusion The use of DMPA before achievement of peak bone mass may be particularly detrimental to bone, but switching DMPA with the OCP in these women does not seem to confer specific benefit in terms of bone density. This needs to be taken into consideration when a change in contraceptive is considered purely for the sake of bone protection.

Bone metabolism markers predict increase in bone mass, height and sitting height during puberty depending on the VDR Fok1 genotype

Longitudinal growth and bone mass accumulation are two important phenomena during puberty, resulting in attainment of peak bone mass (PBM) and final height. They are thought to be under strong genetic control, with the vitamin D receptor (VDR) gene being among the candidate genes. Bone metabolism markers are reported to be good predictors of longitudinal growth and bone mass increase. The purpose of this longitudinal study was to evaluate whether bone metabolism markers predict bone mass and height increase differently according to Fok1 VDR genotype throughout puberty in healthy adolescents. At the start of the study 130 girls were aged 10.8 (range 8.5-12.8) years and 125 boys were aged 11.8 (range 9.4-14.6) years at the first visit. Markers of bone formation and bone resorption were measured at the first visit, as well as height and sitting height (SH), and bone mineral content (BMC) of the lumbar spine, femur, arm and total body. All measurements were repeated after 2 years. A higher BMC of the femur, distal arm and total body was found in ff boys at the first visit, which was not related to higher levels of bone metabolism markers in this group. In girls, no differences between genotypes were seen in BMC (increase). However, concentrations of markers of bone formation [alkaline phosphatase (AP), bone-specific alkaline phosphatase (BAP), procollagen aminoterminal propeptide (PINP)] and bone resorption [type I carboxyterminal telopeptide (ICTP)] were higher in ff girls. Regression coefficients between bone metabolism markers and bone mass increase differed according to genotype and sex. A similar pattern was found for height and SH (increase), the latter as a representative of growth of the axial skeleton, mainly consisting of cancellous bone. Our data suggest that the predicting capacities of bone metabolism markers on bone mass (increase), height and SH (increase) are genotype dependent. Their use as predictors of final height or PBM therefore remains questionable without knowing the genotype.

A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls – a cross-sectional study

The importance of the seasonal variation of calcitropic hormones to growing skeleton has not been established. We studied whether there exists a seasonal variation in calcitropic hormones, bone mineral density (BMD) and bone remodelling markers in early puberty girls. One hundred and ninety-six girls, mean age 11.4 (sd 0.4) years, in Tanner stage 2 (early puberty) and 3 (mid-puberty) were studied during September to March. The BMD was measured from the lumbar vertebrae and the left femur by dual-energy X-ray absoptiometry. Their serum 25-hydroxyvitamin D (S-25-OHD), serum intact parathyroid hormone (S-iPTH), serum osteocalcin, urinary pyridinoline and urinary deoxypyridinoline were analysed from fasting samples. The concentration of S-25-OHD and serum osteocalcin differed among months (P < 0.01), reflecting a seasonal variation. The parathyroid hormone correlated negatively with S-25-OHD (r -0.325, P < 0.001). Moreover, the BMD in the femur (P = 0.047) and to a lesser extent in vertebrae (P = 0.057) differed between months in early puberty girls but this was not seen in mid-puberty. Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7.0-7.6 % difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

Age of Attainment of Peak Bone Mass Is Site Specific in Swedish Men—The GOOD Study

Results from this study suggest that PBM has been attained in the spine and femoral neck, but not in the radius or tibia, in 18- to 20-year-old men, in which an endosteal contraction and increase in cortical volumetric BMD is observed. Peak bone mass (PBM) is an important determinant for the risk of osteoporosis. In men, the age of attainment of PBM has been under some controversy. The objective of this study was to determine if peak bone mass had been attained, and whether it is site specific, in 18- to 20-year-old Swedish men. The Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study consists of 1068 men, 18.9 +/- 0.6 years of age. BMD was measured using both DXA and pQCT. Environmental factors, such as dietary intake and physical activity, were assessed through questionnaires. The independent predictors of BMD were assessed through multiple linear regression, including age, height, weight, calcium intake, smoking, and physical activity. We show, in a large well-characterized cohort, that age was not an independent predictor of BMD of the lumbar spine, femoral neck, or total body, indicating that peak BMD has been achieved in these skeletal sites, whereas it was an independent predictor of BMD of the radius, suggesting that peak BMD has not yet been attained in the long bones. pQCT analyses of the radius and the tibia revealed that age was associated with cortical volumetric BMD and endosteal contraction of the radius and tibia. These results show that the age of attainment of PBM is site specific.

Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia

Adaptation to mechanical loading has been studied extensively in cortical, but not cancellous bone. However, corticocancellous sites are more relevant to osteoporosis and related fracture risk of the hip and spine. We tested the hypotheses that adaptation in a long bone would be greater at cancellous than cortical sites and would depend on the term of daily in vivo cyclic axial loading. We applied compressive loads to the adolescent, 10-week old, male C57BL/6 mouse tibia to examine the skeletal response immediately prior to attainment of peak bone mass. Adaptation was quantified at the completion of either 2-week ( n = 8) or 6-week ( n = 12) loading terms by directly comparing volumetric bone mineral content between loaded and contralateral limbs by microcomputed tomography. The increase in mineral content was site specific with a greater response found in the corticocancellous proximal metaphysis (14%) than the cortical mid-shaft (2%) after 6 weeks of loading. Furthermore, bone volume fraction and average trabecular thickness of cancellous bone in the proximal tibia increased after 6 weeks by 15% and 12% respectively. Diaphyseal response was only evident proximal to the mid-shaft as indicated by an 8% increase in maximum principal moment of inertia. Both loading terms produced similar results for mineral content, volume fraction, and moments of inertia. Our finding that non-invasive loading increases the bone volume and fraction at a corticocancellous site by as much as 15% motivates exploring the use of mechanical loading to attain greater peak bone mass and inhibit osteoporosis.