Menstrual dysfunction and bone health in female athletes

Female athletes are generally considered to be at Iow risk of osteoporosis because of the skeletal loading associated with sports participation. Sites that are exposed to long-term high-impact loading are consistently reported to be higher than the same sites in their sedentary peers. However, weight-bearing exercise does not always ensure that athletes will have high bone-mineral density, as the hormonal environment, dietary factors, and loading history all influence bone-mineral density, In particular, menstrual dysfunction, which can occur with intense training or disordered eating, is a significant risk factor for Iow bone-mineral density. Exercise history before menstrual dysfunction is likely to offer some protection for Iow bone-mineral density, particularly at the hip, Resumption of menses is unlikely to restore bone-mineral density to levels reported in eumenorrheic athletes or even sedentary peers, Athletes at risk of amenorrhea should be identified and their training loads and energy intakes monitored to ensure normal menstrual function, Athletes who remain amenorrheic should be counseled about the possible negative effects of amenorrhea and monitored for bone loss. Early intervention is recommended for amenorrheic athletes with Iow bone-mineral density.

The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8-17 years. Periosteal (external) cross-sectional area (CSA), cortical area, medullary area, and the polar second moments of area (I_p, mm⁴) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and I _p of the humerus were 11-14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri- or postpubertal players despite longer duration of loading (both, _p < 0.01). The higher BMC was the result of a 7-11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone's resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone's rt.osistance to torsion is achieved hy modifying bone shape and mass, not necessarily bone density.

The relationship between muscle size and bone geometry during growth and in response to exercise

As muscles become larger and stronger during growth and in response to increased loading, bones should adapt by adding mass, size, and strength. In this unilateral model, we tested the hypothesis that (1) the relationship between muscle size and bone mass and geometry (nonplaying arm) would not change during different stages of puberty and (2) exercise would not alter the relationship between muscle and bone, that is, additional loading would result in a similar unit increment in both muscle and bone mass, bone size, and bending strength during growth. We studied 47 competitive female tennis players aged 8–17 years. Total, cortical, and medullary cross-sectional areas, muscle area, and the polar second moment of area (Ip) were calculated in the playing and nonplaying arms using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects: In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was linearly associated BMC, total and cortical area, and Ip (r = 0.56–0.81, P < 0.09 to < 0.001), independent of age. No detectable differences were found between pubertal groups for the slope of the relationship between muscle and bone traits. Post-pubertal players, however, had a higher BMC and cortical area relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players had a greater medullary area relative to muscle area than post-pubertal players (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side differences revealed that muscle and bone traits were 6–13% greater in the playing arm in pre-pubertal players, and did not increase with advancing maturation. In all players, the percent (and absolute) side-to-side differences in muscle area were positively correlated with the percent (and absolute) differences in BMC, total and cortical area, and Ip (r = 0.36–0.40, P < 0.05 to < 0.001). However, the side-to-side differences in muscle area only accounted for 11.8–15.9% of the variance of the differences in bone mass, bone size, and bending strength. This suggests that other factors associated with loading distinct from muscle size itself contributed to the bones adaptive response during growth. Therefore, the unifying hypothesis that larger muscles induced by exercise led to a proportional increase in bone mass, bone size, and bending strength appears to be simplistic and denies the influence of other factors in the development of bone mass and bone shape.

Does high-intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes?

The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program (RT+WLoss) could maintain bone mineral density (BMD) and lean mass compared to moderate weight loss (WLoss) alone in older overweight adults with type 2 diabetes. We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program. This was a 12-month trial in which 36 sedentary, overweight adults aged 60 to 80 years with type 2 diabetes were randomized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months (phase 1). Thereafter, all participants completed an additional 6-month home-based training without further dietary modification (phase 2). Total body and regional BMD and bone mineral content (BMC), fat mass (FM) and lean mass (LM) were assessed by DXA every 6 months. Diet, muscle strength (1-RM) and serum total testosterone, estradiol, SHBG, insulin and IGF-1 were measured every 3 months. No between group differences were detected for changes in any of the hormonal parameters at any measurement point. In phase 1, after 6 months of gymnasium-based training, weight and FM decreased similarly in both groups (P<0.01), but LM tended to increase in the RT+WLoss (n=16) relative to the WLoss (n=13) group [net difference (95% CI), 1.8% (0.2, 3.5), P<0.05]. Total body BMD and BMC remained unchanged in the RT+WLoss group, but decreased by 0.9 and 1.5%, respectively, in the WLoss group (interaction, P<0.05). Similar, though non-significant, changes were detected at the femoral neck and lumbar spine (L2-L4). In phase 2, after a further 6 months of home-based training, weight and FM increased significantly in both the RT+WLoss (n=14) and WLoss (n=12) group, but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months. These results indicate that in older, overweight adults with type 2 diabetes, dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health.

Near normalisation of lumbar spine bone density in young women with osteopenia recovered from adolescent onset anorexia nervosa: a longitudinal study

To investigate the effect of the progression of adolescent onset anorexia nervosa (AN) on bone parameters we followed two cohorts (Disease cohort and recovered cohort) of adolescents for a total of 5.2 years. In the 'Disease' cohort (n = 18), lumbar spine bone density (BMD) was reduced by 0.6 SD after 0.8 years of disease and was reduced a further 1.0 SD after a total 2.5 years of disease (p < 0.001). At the third lumbar vertebra there was bone loss (-3.7%, p < 0.05) resulting in reduced volumetric BMD (-5.1%, p < 0.08). In the 'recovered' cohort, lumbar spine BMD was reduced by 1.9 SD after 1.7 years of disease, and increased by 1.5 SD after 2.7 years of recovery (p < 0.001). At the third lumbar vertebra there was an increase in bone mass (20.5%, p < 0.001) and bone volume (14.1%, p < 0.001), resulting in increased volumetric BMD (6.3%, p < 0.08). Normalisation of lumbar spine BMD may be achieved in patients with adolescent onset AN when the successful recovery of body weight is combined with the return of regular menses.

Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men

Introduction: It remains uncertain whether long-term participation in regular weight-bearing exercise confers an advantage to bone structure and strength in old age. The aim of this study was to investigate the relationship between lifetime sport and leisure activity participation on bone material and structural properties at the axial and appendicular skeleton in older men (>50 years).

Methods: We used dual-energy X-ray absorptiometry (DXA) to assess hip, spine and ultradistal (UD) radius areal bone mineral density (aBMD) (n=161), quantitative ultrasound (QUS) to measure heel bone quality (n=161), and quantitative computed tomography (QCT) to assess volumetric BMD, bone geometry and strength at the spine (L₁–L₃) and mid-femur (n=111). Current (>50+ years) and past hours of sport and leisure activity participation during adolescence (13–18 years) and adulthood (19–50 years) were assessed by questionnaire. This information was used to calculate the total time (min) spent participating in sport and leisure activities and an osteogenic index (OI) score for each participant, which provides a measure of participation in weight-bearing activities.

Results: Regression analysis revealed that a greater lifetime (13–50+ years) and mid-adulthood (19–50 years) OI, but not total time (min), was associated with a greater mid-femur total and cortical area, cortical bone mineral content (BMC), and the polar moment of inertia (I _p) and heel VOS (p ranging from <0.05 to <0.01). These results were independent of age, height (or femoral length) and weight (or muscle cross-sectional area). Adolescent OI scores were not found to be significant predictors of bone structure or strength. Furthermore, no significant relationships were detected with areal or volumetric BMD at any site. Subjects were then categorized into either a high (H) or low/non-impact (L) group during adolescence (13–18 years) and adulthood (19–50+ years) according to their OI scores during each of these periods. Three groups were subsequently formed to reflect weight-bearing impact categories during adolescence and then adulthood: LL, HL and HH. Compared to the LL group, mid-femur total and cortical area, cortical BMC and I _p were 6.5–14.2% higher in the HH group. No differences were detected between the LL and HL groups.

Conclusions: In conclusion, these findings indicate that long-term regular participation in sport and leisure activities categorized according to an osteogenic index [but not the total time (min) spent participating in all sport and leisure activities] was an important determinant of bone size, quality and strength, but not BMD, at loaded sites in older men. Furthermore, continued participation in weight-bearing exercise in early to mid-adulthood appears to be important for reducing the risk of low bone strength in old age.

Calcium- and vitamin D3 - fortified milk reduces bone loss at clinically relevant skeletal sites on llder men: a 2-year randomised controlled trial

In this 2-year randomized controlled study of 167 men >50 years of age, supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinically important skeletal sites at risk for fracture.

Introduction: Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis. The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men >50 years of age.

Materials and Methods: This was a 2-year randomized controlled study in which 167 men (mean age ± SD, 61.9 ± 7.7 years) were assigned to receive either 400 ml/day of reduced fat (1%) ultra-high temperature (UHT) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk. Primary endpoints were changes in BMD, serum 25(OH)D, and PTH.

Results: One hundred forty-nine men completed the study. Baseline characteristics between the groups were not different; mean dietary calcium and serum 25(OH)D levels were 941 ± 387 mg/day and 77 ± 23 nM, respectively. After 2 years, the mean percent change in BMD was 0.9-1.6% less in the milk supplementation compared with control group at the femoral neck, total hip, and ultradistal radius (range, p < 0.08 to p < 0.001 after adjusting for covariates). There was a greater increase in lumbar spine BMD in the milk supplementation group after 12 and 18 months (0.8-1.0%, p ≤ 0.05), but the between-group difference was not significant after 2 years (0.7%; 95% CI, −0.3, 1.7). Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year (31% and −18%, respectively; both p < 0.001), and these differences remained after 2 years. Body weight remained unchanged in both groups at the completion of the study.

Conclusions: Supplementing the diet of men >50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple, nutritionally sound and cost-effective strategy to reduce age-related bone loss at several skeletal sites at risk for fracture in the elderly.

Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men

The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known. The aim of this study was to examine the effects of high calcium (1000 mg/day)- and vitamin-D3 (800 IU/day)-fortified milk on cortical and trabecular volumetric BMD (vBMD) and bone geometry at the axial and appendicular skeleton in men aged over 50 years. One hundred and eleven men who were part of a larger 2-year randomized controlled trial had QCT scans of the mid-femur and lumbar spine (L1–L3) to assess vBMD, bone geometry and indices of bone strength [polar moment of inertia (Ipolar)]. After 2 years, there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L1–L3 bone parameters for all men aged over 50 years. However, the mid-femur skeletal responses to the fortified milk varied according to age, with a split of ≤62 versus >62 years being the most significant for discriminating the changes between the two groups. Subsequent analysis revealed that, in the older men (>62 years), the expansion in mid-femur medullary area was 2.8% (P < 0.01) less in the milk supplementation compared to control group, which helped to preserve cortical area in the milk supplementation group (between group difference 1.1%, P < 0.01). Similarly, for mid-femur cortical vBMD and Ipolar, the net loss was 2.3 and 2.8% less in the milk supplementation compared to control group (P < 0.01 and <0.001, respectively). In conclusion, calcium–vitamin-D3-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men.

Elastic modulus and hardness of cortical and trabecular bovine bone measured by nanoindentation

The elastic modulus and hardness of several microstructure components of dry bovine vertebrae and tibia have been investigated in the longitude and transverse directions using nanoindentation. The elastic modulus for the osteons and the interstitial lamellae in the longitude direction were found to be (24.7±2.5) GPa and (30.1±2.4) GPa. As it's difficult to distinguish osteons from interstitial lamellae in the transverse direction, the average elastic modulus for cortical bovine bone in the transverse direction was (19.8±1.6) GPa. The elastic modulus for trabecular bone in the longitude and transverse direction were (20±2) GPa and (14.7±1.9) GPa respectively. The hardness also varied among the microstructure components in the range of 0.41–0.89 GPa. Analyses of variance show that the values are significantly different.

Novel titanium foam for bone tissue engineering

Titanium foams fabricated by a new powder metallurgical process have bimodal pore distribution architecture (i.e., macropores and micropores), mimicking natural bone. The mechanical properties of the titanium foam with low relative densities of approximately 0.20-0.30 are close to those of human cancellous bone. Also, mechanical properties of the titanium foams with high relative densities of approximately 0.50-0.65 are close to those of human cortical bone. Furthermore, titanium foams exhibit good ability to form a bonelike apatite layer throughout the foams after pretreatment with a simple thermochemical process and then immersion in a simulated body fluid. The present study illustrates the feasibility of using the titanium foams as implant materials in bone tissue engineering applications, highlighting their excellent biomechanical properties and bioactivity.

Determinants of bone density in 30- to 65-year-old women: A co-twin study

Introduction: Reported effects of body composition and lifestyle of bone mineral density in pre-elderly adult women have been inconsistent.

Methods: In a co-twin study of 146 female twin pairs aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar spine, total hip, and forearm, total body bone mineral content, and lean and fat mass. Height and weight were measured. Menopausal status, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Within-pair differences in bone measures were regressed through the origin against within-pair differences in putative determinants.

Results: Lean mass and fat mass were associated with greater bone mass at all sites. A discordance of 10 pack-years smoking was related to a 2.3-3.3% (SE, 0.8-1.0) decrease in bone density at all sites except the forearm, with the effects more evident in postmenopausal women. In all women, a 0.8% (SE, 0.3) difference in hip bone mineral density was associated with each hour per week difference in sporting activity, with effects more evident in premenopausal women. Daily dietary calcium intake was related to total body bone mineral content and forearm bone mineral density (1.4 ± 0.7% increase for every 1000 mg). Lifetime alcohol consumption and walking were not consistently related to bone mass.

Conclusion: Several lifestyle and dietary factors, in particular tobacco use, were related to bone mineral density. Effect sizes varied by site. Characterization of determinants of bone mineral density in midlife and thereafter may lead to interventions that could minimize postmenopausal bone loss and reduce osteoporotic fracture risk.

Tyrosine residues of the granulocyte colony-stimulating factor transmit proliferation and differentiation signals in murine bone marrow cells

Granulocyte colony-stimulating factor (G-CSF) is the major regulator of granulopoiesis and acts through binding to its specific receptor (G-CSF-R) on neutrophilic granulocytes. Previous studies of signaling from the 4 G-CSF-R cytoplasmic tyrosine residues used model cell lines that may have idiosyncratic, nonphysiological responses. This study aimed to identify specific signals transmitted by the receptor tyrosine residues in primary myeloid cells. To bypass the presence of endogenous G-CSF-R, a chimeric receptor containing the extracellular domain of the epidermal growth factor receptor in place of the entire extracellular domain of the G-CSF-R was used. A series of chimeric receptors containing tyrosine mutations to phenylalanine, either individually or collectively, was constructed and expressed in primary bone marrow cells from G-CSF-deficient mice. Proliferation and differentiation responses of receptor-expressing bone marrow cells stimulated by epidermal growth factor were measured. An increased 50% effective concentration to stimulus of the receptor Ynull mutant indicated that specific signals from tyrosine residues were required for cell proliferation, particularly at low concentrations of stimulus. Impaired responses by mutant receptors implicated G-CSF-R Y764 in cell proliferation and Y729 in granulocyte differentiation signaling. In addition, different sensitivities to ligand stimulation between mutant receptors indicated that G-CSF-R Y744 and possibly Y729 have an inhibitory role in cell proliferation. STAT activation was not affected by tyrosine mutations, whereas ERK activation appeared to depend, at least in part, on Y764. These observations have suggested novel roles for the G-CSF-R tyrosine residues in primary cells that were not observed previously in studies in cell lines.

Interaction between playing golf and HRT on vertebral bone properties in post-menopausal women measured by QCT

Summary We investigated the effect of playing regular golf and HRT on lumbar and thoracic vertebral bone parameters (measured by QCT) in 72 post-menopausal women. The main finding of this study was that there was positive interaction between golf and HRT on vertebral body CSA and BMC at the thoracic 12 and lumbar 2 vertebra but not the third and seventh thoracic vertebras.

Introduction Identifying specific exercises that load the spine sufficiently to be osteogenic is an important component of primary osteoporosis prevention. The aim of this study was to determine if in postmenopausal women regular participation in golf resulted in greater paravertebral muscle mass and improved vertebral bone strength.

Methods Forty-seven postmenopausal women who played golf regularly were compared to 25 controls. Bone parameters at the mid-vertebral body were determined by QCT at spinal levels T3, T7, T12 and L2 (cross-sectional area (CSA), total volumetric BMD (vBMD), trabecular vBMD of the central 50% of total CSA, BMC and cortical rim thickness). At T7 and L2, CSA of trunk muscles was determined.

Results There was a positive interaction between golf and HRT for vertebral CSA and BMC at T12 and L2, but not at T3 or T7 (p ranging < 0.02 to 0.07). Current HRT use was associated with a 10–15% greater total and trabecular vBMD at all measured vertebral levels. Paravertebral muscle CSA did not differ between groups. Vertebral CSA was the bone parameter significantly related to muscle CSA.

Conclusion These findings provide preliminary evidence that playing golf may improve lower spine bone strength in postmenopausal women who are using HRT.