Effects of the Type of Exercise Training on Bone Health Parameters in Adolescent Girls: A Systematic Review.

Interventional studies offer strong evidence for exercise's osteogenic impact on bone particularly during growth. With rising osteoporosis rates in older women, enhancing bone strength early in life is crucial. Thus, investigating the osteogenic effects of different types of physical activities in young females is crucial. Despite varied findings, only two systematic reviews tried to explore this topic without examining how different types of exercise may affect bone health in adolescent girls. The first aim of this systematic review was to assess the impact of exercise training on bone health parameters in adolescent girls, and the second aim was to investigate whether the type of exercise training can modulate this effect. A systematic literature search was conducted using common electronic databases from inception - January 2023. Seven studies (355 participants) were eligible for inclusion in this systematic review. Two studies dealt with resistance training, 3 studies applied plyometric training, 1 study used team sports, and 1 study used dancing. Results indicate that plyometric training increases lumbar spine bone mass in adolescent girls. Well-designed randomized controlled trials with a proper training period (> 12 weeks) are needed to advocate a specific type of training which has the highest osteogenic effect.

LOX overexpression programming mediates the osteoclast mechanism of low peak bone mass in female offspring rats caused by pregnant dexamethasone exposure.

BACKGROUND: Osteoporosis is a degenerative disease characterized by reduced bone mass, with low peak bone mass being the predominant manifestation during development and having an intrauterine origin. Pregnant women at risk of preterm delivery are commonly treated with dexamethasone to promote fetal lung development. However, pregnant dexamethasone exposure (PDE) can lead to reduced peak bone mass and susceptibility to osteoporosis in offspring. In this study, we aimed to investigate the mechanism of PDE-induced low peak bone mass in female offspring from the perspective of altered osteoclast developmental programming. METHODS: 0.2 mg/kg.d dexamethasone was injected subcutaneously into rats on gestation days (GDs) 9-20. Some pregnant rats were killed at GD20 to remove fetal rat long bones, the rest were delivered naturally, and some adult offspring rats were given ice water swimming stimulation for two weeks. RESULTS: The results showed that the fetal rat osteoclast development was inhibited in the PDE group compared with the control group. In contrast, the adult rat osteoclast function was hyperactivation with reduced peak bone mass. We further found that the promoter region methylation levels of lysyl oxidase (LOX) were decreased, the expression was increased, and the production of reactive oxygen species (ROS) was raised in PDE offspring rat long bone before and after birth. Combined in vivo and in vitro experiments, we confirmed that intrauterine dexamethasone promoted the expression and binding of the glucocorticoid receptor (GR) and estrogen receptor ß (ERß) in osteoclasts and mediated the decrease of LOX methylation level and increase of expression through upregulation of 10-11 translocator protein 3 (Tet3). CONCLUSIONS: Taken together, we confirm that dexamethasone causes osteoclast LOX hypomethylation and high expression through the GR/ERß/Tet3 pathway, leading to elevated ROS production and that this intrauterine epigenetic programming effect can be carried over to postnatal mediating hyperactivation in osteoclast and reduced peak bone mass in adult offspring. This study provides an experimental basis for elucidating the mechanism of osteoclast-mediated intrauterine programming of low peak bone mass in female offspring of PDE and for exploring its early targets for prevention and treatment. Video Abstract.

The Effects of a 1-Year Recreational Kung Fu Protocol on Bone Health Parameters in a Group of Healthy Inactive Young Men.

The main aim of the current study was to explore the effects of a 1-year recreational Kung Fu protocol on bone health parameters (bone mineral content (BMC), bone mineral density (BMD), femoral neck geometry and composite indices of femoral neck strength) in a group of healthy inactive young men. 54 young inactive men voluntarily participated in this study, but only 51 of them completed it. The participants were assigned to 2 different groups: control group (n=31) and Kung Fu group (n=20). The Kung Fu group performed two sessions of recreational Kung Fu per week; the duration of each session was 45 minutes. The current study has demonstrated that whole body (WB) BMC, ultra-distal (UD) radius BMD, 1/3 radius BMD, total radius BMD, total forearm BMD, maximal strength, maximum oxygen consumption and jumping performance increased in the Kung Fu group but not in the control group. The percentages of variations in WB BMC, forearm BMD and physical performance parameters were significantly different between the two groups. In conclusion, this study suggests that recreational Kung Fu is an effective method to improve WB BMC, forearm BMD and physical performance parameters in young inactive men.

It starts from the womb: maximizing bone health.

The foundation of bone health is established in utero. Bone accrual starts from the developing fetus and continues throughout childhood and adolescence. This process is crucial to achieve peak bone mass. Understanding factors that influence bone accrual before attainment of peak bone mass is thus critical to improve bone health and prevent osteoporosis, thereby reducing the burden of osteoporotic fractures in older women. In this review, we broadly outline factors influencing peak bone mass from pregnancy to infancy, childhood and adolescence with potential diseases and medications that may affect the optimum trajectory to maximizing bone health. It is estimated that a 10% increase in peak bone mass will delay the onset of osteoporosis by 13 years in a woman.

Effects of Different Levels of Weightlifting Training on Bone Mineral Density in a Group of Adolescents.

The aim of the current study was to evaluate the effects of different levels of weightlifting training on bone mineral density (BMD) at different body sites (whole body (WB), lumbar spine (LS), femoral neck (FN), upper limbs (UL) and lower limbs (LL)) in a group of adolescents. Three groups of pubertal boys aged 13-15 years were recruited, including a control group (which included 13 untrained adolescents), a moderately trained group (which included 13 non-elite weightlifters, with four sessions of 2 hours per week) and a highly trained group (which included 13 elite weightlifters, with eight sessions of 2 hours per week). The three groups were paired for age and maturation index (using Tanner stages). Body composition, bone mineral content (BMC) and BMD were evaluated by dual-energy X ray absorptiometry (DXA). Physical performance variables (including weightlifting specific exercises, counter movement jump and squat jump) were measured using validated methods. Results showed that the values of BMD and physical performance variables were greater in the group of elite weightlifters compared to the group of non-elite weightlifters and the control group. In addition, the values of BMD and physical performance variables were higher in the group of the non-elite weightlifters compared to those of the control group. After adjusting for lean mass and squat jump, lumbar spine BMD, FN BMD, UL BMD and LL BMD remained significantly higher in the elite weightlifters' group compared to the two other groups. In conclusion, the current study suggests that elite adolescent weightlifters have greater bone health parameters compared to moderately-trained adolescent weightlifters and untrained adolescents.

Pegvisomant in the treatment of acromegaly.

Despite improvements in surgical techniques, current radiotherapy options and development of long-acting somatostatin analogues, biochemical control of acromegaly is not achieved in some patients. The failure to achieve optimal serum growth hormone (RH) and insulin-like growth factor-1 (IGF-1) levels means increased morbidity and mortality of acromegaly patients. The RH receptor antagonist pegvisomant (PEG) is a genetically engineered RH analog that prevents of RH receptor dimerization, i.e. a process that is crucial for the action of RH at the cellular level. The effect of the treatment is suppression of IGF-1 production. In pilot studies, normalization of IGF-1 levels was achieved in up to 90 % of patients receiving PEG. However, PEG efficacy in clinical settings is slightly lower (65 to 97 %) than reported in the key studies. A rare side effect of treatment is elevations of liver transaminases. In addition, pituitary tumor growth progression has been reported in several cases. In this review article, we present long-term data on pegvisomant treatment and discuss its associated risks and benefits.

The frequency window effect of sinusoidal electromagnetic fields in promoting osteogenic differentiation and bone formation involves extension of osteoblastic primary cilia and activation of protein kinase A.

Electromagnetic fields (EMFs) have emerged as a versatile means for osteoporosis treatment and prevention. However, its optimal application parameters are still elusive. Here, we optimized the frequency parameter first by cell culture screening and then by animal experiment validation. Osteoblasts isolated from newborn rats (ROBs) were exposed 90 min/day to 1.8 mT SEMFs at different frequencies (ranging from 10 to 100 Hz, interval of 10 Hz). SEMFs of 1.8 mT inhibited ROB proliferation at 30, 40, 50, 60 Hz, but increased proliferation at 10, 70, 80 Hz. SEMFs of 10, 50, and 70 Hz promoted ROB osteogenic differentiation and mineralization as shown by alkaline phosphatase (ALP) activity, calcium content, and osteogenesis-related molecule expression analyses, with 50 Hz showing greater effects than 10 and 70 Hz. Treatment of young rats with 1.8 mT SEMFs at 10, 50, or 100 Hz for 2 months significantly increased whole-body bone mineral density (BMD) and femur microarchitecture, with the 50 Hz group showing the greatest effect. Furthermore, 1.8 mT SEMFs extended primary cilia lengths of ROBs and increased protein kinase A (PKA) activation also in a frequency-dependent manner, again with 50 Hz SEMFs showing the greatest effect. Pretreatment of ROBs with the PKA inhibitor KT5720 abolished the effects of SEMFs to increase primary cilia length and promote osteogenic differentiation/mineralization. These results indicate that 1.8 mT SEMFs have a frequency window effect in promoting osteogenic differentiation/mineralization in ROBs and bone formation in growing rats, which involve osteoblast primary cilia length extension and PKA activation.

The Relationships Between Skeletal Muscle Index and Bone Variables in a Group of Young Adults.

The purpose of this study was to investigate the relationships between skeletal muscle index (SMI) and bone variables in a group of young adults. Three hundred and thirty-five young adults (129 men and 206 women) whose ages ranged from 18 to 35 yr voluntarily participated in this study. Weight and height were measured, and body mass index (BMI) was calculated. Body composition, bone mineral content (BMC), bone mineral density (BMD), geometric indices of hip bone strength and trabecular bone score (TBS) were determined for each individual by Dual-energy X-ray absorptiometry (DXA). Appendicular skeletal mass (ASM, in kg) was calculated by summing the muscle masses of the 4 limbs, assuming that all nonfat and nonebone mass is skeletal muscle. Skeletal muscle index (SMI) was defined as ASM/height². In young men, SMI was positively correlated to WB BMC (r = 0.63; p < 0.001), WB BMD (r = 0.53; p < 0.001), L1-L4 BMC (r = 0.33; p < 0.001), L1-L4 BMD (r = 0.30; p < 0.001), L1-L4 TBS (r = 0.26; p < 0.01), TH BMC (r = 0.61; p < 0.001), TH BMD (r = 0.46; p < 0.001), FN BMC (r = 0.51; p < 0.001), FN BMD (r = 0.46; p < 0.001), FN cross-sectional area (CSA) (r = 0.56; p < 0.001), FN cross-sectional moment of inertia (CSMI) (r = 0.52; p < 0.001) and FN section modulus (Z) (r = 0.54; p < 0.001) but negatively correlated to FN strength index (SI) (r = -0.24; p < 0.01). In young women, SMI was positively correlated to WB BMC (r = 0.61; p < 0.001), WB BMD (r = 0.60; p < 0.001), L1-L4 BMC (r = 0.35; p < 0.001), L1-L4 BMD (r = 0.33; p < 0.001), L1-L4 TBS (r = 0.29; p < 0.001), TH BMC (r = 0.61; p < 0.001), TH BMD (r = 0.53; p < 0.001), FN BMC (r = 0.45; p < 0.001), FN BMD (r = 0.49; p < 0.001), FN CSA (r = 0.60; p < 0.001), FN CSMI (r = 0.52; p < 0.001), and FN Z (r = 0.40; p < 0.001) but negatively correlated to FN SI (r = -0.20; p < 0.01). The current study suggests that SMI is a positive determinant of bone mineral density and geometric indices of hip bone strength in young adults.

Lifestyle and Environmental Factors Affecting Bone Mass in Japanese Female Adolescents.

PURPOSE: A higher peak bone mass (PBM) in adolescence lowers the risk of osteoporosis later in life. This study examined the factors affecting bone mass in female adolescents in relation to lifestyle and environmental factors to promote bone mass development before reaching PBM. DESIGN AND METHODS: The subjects were female students aged 15-16 years and their mothers at a public high school in Osaka, Japan. Bone mass was measured using quantitative ultrasound parameters. The body composition was measured using a multi-frequency segmental body composition analyzer. Nutrient intake, exercise habits, and maternal factors as environmental factors were examined using a questionnaire. RESULTS: Logistic regression analyses revealed that the adolescents' lean mass was significantly related to the BUA (p < .05). The adjusted odds ratio was 1.29 (95% confidence interval [CI]: 1.07-1.54). In contrast, the adolescents' exercise habit was significantly related to the SOS (p < .05). The SOS was significantly higher in the adolescents who exercised >4 times a week than in those who exercised <2-3 times a week. The adjusted odds ratio was 2.83 (95% CI: 1.06-7.56). The adolescents' nutrient intake and maternal factors were not significant factors affecting the adolescents' bone mass. CONCLUSIONS: The present study suggests that increasing lean mass and exercising more than four times a week were important for increasing bone mass in female adolescents. PRACTICE IMPLICATIONS: Nurses should intervene to help female adolescents acquire healthy lifestyle skills and maintain proper body composition and exercise habits to promote bone mass development before reaching PBM.

Age- and Strain-Related Differences in Bone Microstructure and Body Composition During Development in Inbred Male Mouse Strains.

We explored age- and strain-related differences in bone microstructure and body composition in male C57BL/6J, DBA/2JRj and C3H/J mice. Bone microstructure of the femur, tibia and L4 was assessed by µCT at the age of 8, 16 and 24 weeks. The weight of several muscles and fat depots were measured at the same time points. At all timepoints, C3H/J mice had the thickest cortices followed by DBA/2JRj and C57BL/6J mice. Nevertheless, C57BL/6J mice had higher Tb.BV/TV and Tb.N, and lower Tb.Sp than DBA/2JRj and C3H/J mice at least at 24 weeks of age. Skeletal development patterns differed among strains. C57BL/6J and DBA/2JRj mice, but not C3H/J mice, experienced significant increases in the sum of the masses of 6 individual muscles by 24 weeks of age. In C57BL/6J and DBA/2JRj mice, the mass of selected fat depots reached highest values at 24 weeks, whist, in C3H/J mice, the highest values of fat depots masses were achieved at 16 weeks. Early strain differences in muscle and fat masses were largely diminished by 24 weeks of age. C3H/J and C57BL/6J mice displayed the most favorable cortical and trabecular bone parameters, respectively. Strain differences in body composition were less overt than strain specificity in bone microstructure, however, they possibly influenced aspects of skeletal development.

Oral contraceptive use, bone mineral density, and bone turnover markers over 12 months in college-aged females.

INTRODUCTION: The purpose of this study was to compare bone mineral density (BMD) and bone turnover markers between combined oral contraceptive (COC) and non-COC users over 12 months. MATERIALS AND METHODS: COC users (n = 34, age = 19.2 ± 0.5) and non-COC users (n = 28, age = 19.3 ± 0.6) provided serum at baseline, 6 months, and 12 months. C-terminal telopepetides (CTX) and pro-collagen type 1 N-terminal propeptides (P1NP) were determined using ELISA. BMD was measured at the three time points using dual-energy x-ray absorptiometry (DXA). RESULTS: COC users had greater CTX than non-COC users at baseline (18.6 ± 8.2 vs. 13.8 ± 5.3 ng/mL, P = 0.021) and 6 months (20.4 ± 10.3 vs. 14.2 ± 8.5 ng/mL, P = 0.018). Controlling for lean mass, groups were similar in BMD. Over 12 months, non-COC users maintained BMD at the spine, while the COC users declined 2.2% in lateral spine BMD (0.773 ± 0.014 to 0.756 ± 0.014 g/cm2, P = 0.03) and 0.7% in anterior-posterior spine BMD (1.005 ± 0.015 to 0.998 ± 0.015 g/cm2, P = 0.069). Non-COC users increased in BMD of the whole body over 12 months (P < 0.001) while COC users had no change. Women who began COCs within 4 years after menarche had lower BMD at the hip and whole body. Women taking very low dose COCs (20 mcg ethinyl estradiol, EE) significantly declined in CTX, P1NP, and lateral spine BMD in comparison to participants using low dose COCs (30/35 mcg EE). CONCLUSION: College-aged women who did not use COCs increased BMD of the whole body, while COC users had elevated bone turnover, declines in spinal BMD, and lack of bone acquisition of the whole body over 12 months. Young females who initiate COC use early after menarche may experience skeletal detriments.

Exercise and Peak Bone Mass.

PURPOSE OF REVIEW: The main goal of this narrative review is to assess whether physical activity (PA) influences peak bone mass and fracture risk. RECENT FINDINGS: Several randomized controlled trials (RCT) show that short-term PA intervention programs in childhood improve the accrual of bone mineral. There are now also long-term controlled PA intervention studies demonstrating that both boys and girls with daily school PA through puberty gain higher bone mineral content (BMC) and bone mineral density (BMD) and greater bone size than boys and girls with school PA 1-2 times/week. These benefits seem to be followed by a gradual reduction in expected fracture rates, so that in children with daily school PA, the incidence rate ratio (IRR) after 8 years is less than half that expected by age. Daily school PA from before to after puberty is associated with beneficial gains in bone traits and gradually lower relative fracture risk.

Intensity of resistance training via self-reported history is critical in properly characterizing musculoskeletal health.

BACKGROUND: Intensity of resistance training history might be omitted or poorly ascertained in prescreening or data questionnaires involving musculoskeletal health. Failure to identify history of high-versus low-intensity training may overlook higher effect sizes with higher intensities and therefore diminish the precision of statistical analysis with resistance training as a covariate and bias the confirmation of baseline homogeneity for experimental group designation. The purpose was to determine the degree to which a single question assessing participant history of resistance training intensity predicted differences in musculoskeletal health. METHODS: In the first research aim, participants were separated into groups with a history (RT) and no history (NRT) of resistance training. The second research aim evaluated the history of resistance training intensity on muscular strength, lean mass, and bone mineral density (BMD), RT participants were reassigned into a low- (LIRT) or high-intensity resistance training group (HIRT). 83 males and 87 females (19.3 ± 0.6 yrs., 171.1 ± 9.9 cm, 67.1 ± 10.5 kg, 22.9 ± 2.8 BMI, 26.2 ± 7.2% body fat) completed handgrip dynamometry (HG) and dual-energy x-ray absorptiometry scans (DXA) for BMD and bone mineral-free lean mass (BFLM). RESULTS: A 3-group method (NRT, LIRT, HIRT) reduced type-I error compared with the 2-group method (NRT, RT) in characterizing the likely effects of one's history of resistance training. For the second aim, HIRT had significantly (p < 0.05) greater HG strength (76.2 ± 2.2 kg) and arm BFLM (6.10 ± 0.16 kg) than NRT (67.5 ± 1.3 kg; 4.96 ± 0.09 kg) and LIRT (69.7 ± 2.0 kg; 5.42 ± 0.14 kg) while also showing significantly lower muscle quality (HG/BFLM) than NRT (13.9 ± 0.2 vs. 12.9 ± 0.3). HIRT had greater BMD at all sites compared to NRT (whole body = 1.068 ± 0.008 vs. 1.120 ± 0.014; AP spine = 1.013 ± 0.011 vs. 1.059 ± 0.019; lateral spine = 0.785 ± 0.009 vs. 0.846 ± 0.016; femoral neck = 0.915 ± 0.013 vs. 0.970 ± 0.022; total hip = 1.016 ± 0.012 vs. 1.068 ± 0.021 g/cm2) while LIRT revealed no significant skeletal differences to NRT. CONCLUSIONS: Retrospective identification of high-intensity history of resistance training appears critical in characterizing musculoskeletal health and can be ascertained easily in as little as a single, standalone question. Both retrospective-questionnaire style investigations and pre-screening for potential participation in prospective research studies should include participant history of resistance training intensity.

Recognizing the peak bone mass (age 30) as a cutoff point to achieve the success of orthodontic implants.

The aim of present study was to investigate the critical risk factor (age 30: peak bone mass) to evaluate the success of orthodontic implants. A total of 426 orthodontic implants were placed in 270 patients as orthodontic anchorages. Data were analyzed according to patient's characteristics, location of placement, implant categories, and orthodontic force. The young patients were the age ≤ 30 years and the older patients were the age > 30 years. Statistical analysis was performed and a p value < 0.05 was considered to indicate statistical significance. The Chi-square or Fisher exact test was used depending on sample sizes. The null hypothesis was no statistically significant correlation between age ≤ 30 years and age > 30 years. The overall success rate (with and without predrill) was 89.2%. The success rate of orthodontic implants was significantly larger in younger patients (89.9%) than in older patients (76.1%). Recognizing age-related factor in the success rates, older patient (> 30 years) were significant lower than young patients (≤ 30 years) in the gender (female and male), malocclusion (Class II), facial pattern (ortho and hyperdivergent), location (infrazygomatic crest), jaw (maxilla), side (right), material (titanium and stainless), length (9 mm and 10 mm), diameter (2 mm), load (< 3 weeks), and force (intrusion). Therefore, the null hypothesis was rejected. Age 30 is a cutoff point to achieve the success of orthodontic implants. The success rates of older patients (age > 30 years) were significant lower than young patients (age ≤ 30 years), especially in female.

Contraception in adolescents with anorexia nervosa. Is there evidence for a negative impact of combined hormonal contraceptives on bone mineral density and the course of the disease?

Objective: Adolescents with anorexia nervosa (AN) are at increased risk of unplanned pregnancies and bone loss, due to low oestrogen levels and low use of efficient contraception. The negative impact of combined hormonal contraceptives (CHC) on peak bone mass during adolescence might limit wider use in anorexic women. Another issue limiting CHC use is the concern, that CHC-induced cyclic bleeding reduces the motivation for further weight gain and thus exerts a negative impact on recovery. We wanted to find evidence based answers about the impact of CHC use on bone health and course of the disease in adolescents with AN.Methods: We performed a narrative review of the current literature investigating the effect of CHC or progestin-only contraceptives on bone density, body shape and course of disease in young women with anorexia.Results: There is no evidence that CHC use aggravates the bone loss associated with AN. In long-term users CHC exert a protective effect. Anorexic women using CHC showed at least the same or a greater weight gain in comparison with controls. Eating disorder attitudes did not worsen.Conclusion: We conclude, that at present there is no evidence, that use of CHC by AN patients has a negative impact on bone density or the course of disease.

The Association between First Fractures Sustained during Childhood and Adulthood and Bone Measures in Young Adulthood.

OBJECTIVE: To describe the association between fractures sustained at different stages of growth and bone measures in early adulthood. STUDY DESIGN: Participants (n = 201) in southern Tasmania were at birth at a higher risk of sudden infant death syndrome; they were followed to age 25. Outcomes were areal bone mineral density at the spine, hip, and total body (by dual-energy x-ray absorptiometry) and trabecular and cortical bone measures at the radius and tibia (by high-resolution peripheral quantitative computed tomography). Fractures were self-reported and confirmed by radiographs at 8, 16, and 25 years of age. Multivariable linear regression was used to analyze the association of the occurrence of prepubertal (<9 years of age), pubertal (9-16 years of age), and postpubertal (17-25 years of age) fractures with all bone measures. RESULTS: Over 25 years, 99 participants had at least 1 fracture. For high-resolution peripheral quantitative computed tomography measures at age 25, prepubertal fractures were negatively associated with cortical and trabecular volumetric bone mineral density and most microarchitecture measures at both the tibia and radius. Prepubertal fractures had a significant association with smaller increase of areal bone mineral density from age 8 to 16 years and at 25 years of age compared with participants with no fractures. Pubertal fractures had no association with any bone measures and postpubertal fractures were only associated with a lower trabecular number at the tibia. CONCLUSIONS: Prepubertal fractures are negatively associated with areal bone mineral density increases during growth and high-resolution peripheral quantitative computed tomography bone measures in young adulthood. There is little evidence that fractures occurring from age 8 years onward with bone measures in young adulthood, implying that prepubertal fractures may be associated with bone deficits later in life.

Dairy foods and bone health throughout the lifespan: a critical appraisal of the evidence.

The consumption of high-Ca, high-protein dairy foods (i.e. milk, cheese, yogurt) is advocated for bone health across the lifespan to reduce the risk of low-trauma fractures. However, to date, the anti-fracture efficacy of dairy food consumption has not been demonstrated in randomised controlled trials but inferred from cross-sectional and prospective studies. The anti-fracture efficacy of dairy food consumption is plausible, but testing this requires a robust study design to ensure outcomes are suitably answering this important public health question. The evidence of skeletal benefits of dairy food consumption is equivocal, not because it may not be efficacious but because the study design and execution are often inadequate. The key issues are compliance with dietary intervention, dropouts, sample sizes and most importantly lack of deficiency before intervention. Without careful appraisal of the design and execution of available studies, precarious interpretations of outcomes may be made from these poorly designed or executed studies, without consideration of how study design may be improved. Dairy food interventions in children are further hampered by heterogeneity in growth: in particular sex and maturity-related differences in the magnitude, timing, location and surface-specific site of bone accrual. Outcomes of studies combining children of different sexes and maturity status may be masked or exaggerated by these differences in growth, so inaccurate conclusions are drawn from results. Until these critical issues in study design are considered in future dairy food interventions, the anti-fracture efficacy of dairy food consumption may remain unknown and continue to be based on conjecture.

Bone Geometric Properties of the Femoral Neck in Underweight Eumenorrheic Women.

The aim of this study was to describe femoral neck (FN) geometry among eumenorrheic underweight women around the age of peak bone mass. Proximal femur geometry and body composition were assessed in 12 underweight women and in 24 healthy controls using dual-energy X-ray absorptiometry. The Hip Structural Analysis program was used to determine bone geometry at the FN. The cross-sectional area (CSA) and the cross-sectional moment of inertia (CSMI) were significantly lower in underweight women than in controls (p < 0.05). There was a trend toward lower sectional modulus (Z) and strength index in underweight women (p < 0.15). Body weight, body mass index, and lean mass (LM) were positively correlated with CSA, CSMI, Z, and neck-shaft angle (r = 0.428-0.611, p < 0.05). After controlling for body weight, body mass index, and LM, the differences in CSA, CSMI, Z, and neck-shaft angle were no more statistically significant between the 2 groups. The multivariate analysis retained LM as the main predictor of CSA, CSMI, and Z in the whole population. The present study suggests that thinness is associated with low resistance to axial forces (CSA) and bending load (Z and CSMI) in adult eumenorrheic women. LM seems to be a key determinant of FN geometry in underweight women.

Bone loss in C57BL/6J-OlaHsd mice, a substrain of C57BL/6J carrying mutated alpha-synuclein and multimerin-1 genes.

The inbred mouse strain C57BL/6 is commonly used for the generation of transgenic mouse and is a well established strain in bone research. Different vendors supply different substrains of C57BL/6J as wild-type animals when genetic drift did not incur any noticeable phenotype. However, we sporadically observed drastic differences in the bone phenotype of "WT" C57BL/6J mice originating from different labs and speculated that these variations are attributable, at least in part, to the variation between C57BL/6J substrains, which is often overlooked. C57BL/6J-OlaHsd is a commonly used substrain that despite a well defined deletion in the alpha-synuclein (Snca) and multimerin-1 (Mmrn1) genes, was reported to display no obvious phenotype and is used as WT control. Here, we compared the bone phenotype of C57BL/6J-OlaHsd (6J-OLA) to C57BL/6J-RccHsd (6J-RCC) and to the original C57BL/6J (6J-JAX). Using µCT analysis, we found that 6J-OLA mice display a significantly lower trabecular bone mass compared to 6J-RCC and 6J-JAX. PCR analysis revealed that both the Snca and Mmrn1 genes are expressed in bone tissue of 6J-RCC animals but not of 6J-OLA mutants, suggesting either one or both genes play a role in bone metabolism. In vitro analysis demonstrated increase in osteoclasts number and decreased osteoblast mineralization in cells derived from 6J-OLA compared with 6J-RCC. Our data may shed light on unexplained differences in basal bone measurements between different research centers and reiterate the importance of specifying the exact substrain type. In addition, our findings describe the physiological role for Mmrn1 and/or Snca in bone remodeling.

The wakefulness promoting drug Modafinil causes adenosine receptor-mediated upregulation of receptor activator of nuclear factor κB ligand in osteoblasts: Negative impact of the drug on peak bone accrual in rats.

Modafinil is primarily prescribed for treatment of narcolepsy and other sleep-associated disorders. However, its off-prescription use as a cognition enhancer increased considerably, specially among youths. Given its increasing use in young adults the effect of modafinil on peak bone accrual is an important issue but has never been investigated. Modafinil treatment to young male rats caused trabecular and cortical bone loss in tibia and femur, and reduction in biomechanical strength. Co-treatment of modafinil with alendronate (a drug that suppresses bone resorption) reversed the trabecular bone loss but failed to prevent cortical loss. Modafinil increased serum type 1 pro-collagen N-terminal protein (P1NP) and collagen type 1 cross-linked C-telopeptide (CTX-1) indicating a high turnover bone loss. The drug also increased receptor activator of nuclear factor κB ligand (RANKL) to osteoprotegerin (OPG) ratio in serum which likely resulted in increased osteoclast number per bone surface. Furthermore, conditioned medium from modafinil treated osteoblasts increased the expression of osteoclastogenic genes in bone marrow-derived macrophages and the effect was blocked by RANKL neutralizing antibody. In primary osteoblasts, modafinil stimulated cAMP production and using pharmacological approach, we showed that modafinil signalled via adenosine receptors (A2AR and A2BR) which resulted in increased RANKL expression. ZM-241,385 (an A2AR inhibitor) and MRS 1754 (an A2BR inhibitor) suppressed modafinil-induced upregulation of RANKL/OPG ratio in the calvarium of new born rat pups. Our data suggests that by activating osteoblast adenosine receptors modafinil increases the production of osteoclastogenic cytokine, RANKL that in turn results in high turnover bone loss in young rats.