Gender differences in fractures may be related to body size, bone size, geometry, or density. We studied this in 18-year-old males (n = 36) and females (n = 36) matched for height and weight. Despite comparable body size, males have greater BMC and BMD at the hip and distal tibia and greater tibial cortical thickness. This may confer greater skeletal integrity in males.Introduction: Gender differences in fractures may be related to body size, bone size, geometry, or density. We studied this in males (n = 36) and females (n = 36; mean age = 18 years) pair-matched for height and weight.Materials and Methods: BMC, bone area (BA), and BMD were measured in the spine and hip using DXA. Distal tibia was measured by pQCT.Results and Conclusions: Males had a higher lean mass (92%) compared with females (79%). No gender differences were observed for vertebral BMC or vertebral height, although males had greater width and thus BA at the spine. Males had greater BMC and BA at the femoral neck and total femur (P < 0.02). Geometric variables of the hip including neck diameter and neck-axis length were also greater in males (p < 0.02). There was greater cross-sectional moment of inertia, safety factor, and fall index in males (all p < 0.02). Males had greater tibial BMC, volumetric BMD, and cortical area and thickness compared with females (p < 0.01), with both greater periosteal circumference (p = 0.011) and smaller endosteal circumference (p = 0.058). Statistically controlling for lean mass reduced gender differences, but males still had 8% higher hip BMD (p = 0.24) and 5.3% higher total tibial BMD (p = 0.05). A subset of males and females were matched (n = 14 pairs) for total hip BA. Males in this subset still had greater BMC and BMD at the total hip (p < 0.05) than females, despite similar BA. In summary, despite comparable body size, males have greater BMC and BMD than females at the hip and distal tibia but not at the spine. Differences in BMC and BMD were related to greater cortical thickness in the tibia. We conclude that differences in bone mass and geometry confer greater skeletal integrity in males, which may contribute to the lower incidence of stress and osteoporotic fractures in males.

Our best pharmacologic agents for osteoporosis treatment prevent no more than 40‐60% of osteoporotic fractures in patients at highest risk. Thus, there is a need for agents that can further augment bone mass and reduce fracture risk more substantially. To this end, we investigated the utility of parathyroid hormone (PTH) in combination with established hormone‐replacement therapy (HRT) in women with osteoporosis. Fifty‐two women who had been on HRT for at least 2 years were enrolled in this trial in which 25 were assigned randomly to remain on HRT alone and 27 were assigned to remain on HRT and also receive daily subcutaneous PTH(1‐34) 400 U (25 μg) per day for 3 years. Bone mineral density (BMD) measurements at the spine, hip, and total body as well as biochemical determinations of bone turnover and calcium homeostasis were obtained every 6 months. Lateral thoracic and lumbar spine X‐rays were obtained at baseline and annually. Subjects also had measurements of bone density and biochemical indices of bone turnover 1 year after discontinuation of PTH, while HRT was continued. In the group receiving HRT alone, bone density and biochemical variables of bone turnover remained stable throughout the 3‐year treatment trial and 1‐year follow‐up. In the PTH + HRT group, biochemical variables of bone formation and resorption peaked at 6 months and subsequently remained elevated until 30 months at which time levels were indistinguishable from baseline. Subjects in the PTH + HRT group increased bone mass by 13.4 ± 1.4% in the spine, 4.4 ± 1.0% in the total hip, and 3.7 ± 1.4% in the total body. Bone density measurements remained stable 1 year after discontinuation of PTH without any significant loss while women continued HRT. Biochemical variables did not change significantly after cessation of PTH through the 1‐year follow‐up period. PTH + HRT reduced the percent of women who had vertebral fractures from 37.5% to 8.3% (using a 15% height reduction criterion) and from 25% to 0% (using a 20% height reduction criterion) compared with women receiving HRT alone (p < 0.02 for both). We conclude that ongoing HRT maintains almost all of the PTH‐induced bone mass increment for 1 year after discontinuation of PTH. Furthermore, PTH in combination with hormone therapy is an effective means of increasing bone mass throughout the skeleton and specifically reducing vertebral fracture occurrence by 75‐100%, compared with HRT alone.

The use of dual X-ray absorptiometry (DXA) for measurement of bone mineral and body composition in pediatric subjects faces a major technical issue: body size dictates choice of scan mode. However, different scan modes change results in the same subject, thus affecting the accuracy of bone/body composition measurements and especially the capacity to measure changes owing to either growth or intervention. To evaluate the effect of scan mode selections on measurements of bone mineral and body composition, 13 children with weights at the cutoff point between the pediatric large and adult medium scan modes of Lunar DPX or DPXL (Lunar, Madison, WI) with software 3.6 g (35.3 +/- 0.9 kg or 77.7 +/- 2.0 lb) were scanned by both modes. Adult medium mode gave significantly higher results than pediatric large mode for total body fat mass (11.1%), fat% (10.5%), bone mineral content (8.1%), and bone area (1.3%) (p < 0.02). The differences between pediatric large and adult medium modes in fat measurements increased with increasing body mass index ([BMI], kg/m(2)), body surface area ([BSA], m(2)), and trunk size (mm), whereas the differences in bone mineral measurement tended to be greater only with increasing BMI and BSA. None of the differences were correlated to body weight. This study suggests that scan mode selections based on trunk size, BMI, or BSA instead of body weight may improve continuity of bone and body composition measurements by the DXA technique in pediatric subjects.

Dual-energy X-ray absorptiometry (DXA) is rapidly gaining acceptance as a reference method for analyzing body composition. An important and unresolved concern is whether and to what extent variation in soft tissue hydration causes errors in DXA fat estimates. The present study aim was to develop and validate a DXA physical hydration model and then to apply this model by simulating errors arising from hypothetical overhydration states. The DXA physical hydration model was developed by first linking biological substance elemental content with photon attenuation. The validated physical model was next extended to describe photon attenuation changes anticipated when predefined amounts of two known composition components are mixed, as would occur when overhydration develops. Two overhydration models were developed in the last phase of study, formulated on validated physical models, and error was simulated for fluid surfeit states. Results indicate that systematic errors in DXA percent fat arise with added fluids when fractional masses are varied as a percentage of combined fluid + soft tissue mass. Three independent determinants of error magnitude were established: elemental content of overhydration fluid, fraction of combined fluid + soft tissue as overhydration fluid, and initial soft tissue composition. Small but systematic and predictable errors in DXA soft tissue composition analysis thus can arise with fluid balance changes.

Objectives: We have previously shown that MS patients have significantly reduced bone mass and a high prevalence of abnormal vitamin D status. The object of this study was to characterize the frequency of adulthood fractures in MS patients, prospectively determine rates of bone loss in MS, and determine whether vitamin D status is a predictor of bone loss. Methods: MS patients (36 women, 18 men) were compared with age- and gender-matched healthy controls (35 women, 14 men). Bone mass was performed by dual x-ray absorptiometry at baseline and at 12-month intervals over 2 years. Results: Fractures in the absence of major trauma had occurred in 2% of controls and 22% of MS patients (p < 0.002). Over the 2 years of prospective follow-up, both women and men with MS lost substantially more bone in the femoral neck than did controls (3% and 6% per year in pre- and postmenopausal women with MS versus 0.5% and 0.8% per year in controls; 7.3% per year in men with MS versus 1.6% per year in controls). Bone loss in the spine was also greater in women with MS than in controls (1.6 to 3.5% per year loss in MS patients versus no change in controls). Duration of steroid treatment beyond 5 months and ambulatory status were both predictors of bone loss. Bone loss in the spine occurred faster in MS patients with low (<20 ng/mL) 25-hydroxyvitamin D levels (1.9% per year, p < 0.04), whereas in those with normal 25-hydroxyvitamin D levels, bone loss was insignificant. At the femoral neck, bone loss was substantial in all patients, but was somewhat faster in the group with low levels of 25-hydroxyvitamin D (5.6% per year, p < 0.0001) compared with the group with high levels of 25-hydroxyvitamin D (4.3% per year, p = 0.03). Conclusions: MS patients have more frequent fractures and lose bone mass more rapidly than do their healthy age- and gender-matched peers, in part related to insufficient vitamin D. Vitamin D repletion in MS patients who are deficient might reduce, to some extent, the rate of bone loss and decrease osteoporosis-related fractures.

BackgroundSmall increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed.MethodsWe did a 3-year randomised controlled trial to find out the effects of 1–34 human parathyroid hormone (hPTH [1–34], 400 U/25 μg daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n=17). The controls were women taking hormone-replacement therapy only (n=17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints.FindingsPatients taking hormone-replacement therapy and PTH (1–34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13·0% (p<0·001); 2·7% at the hip (p=0·05); and 8·0% in total-body bone mineral (p=0·002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p=0·04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment.InterpretationWe found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.

Does weight-bearing exercise offset bone loss associated with oligomenorrhea? If so, bone mineral density (BMD) will be stable at weight bearing sites but decrease at non-weight-bearing sites with increasing duration of oligomenorrhea. To test this hypothesis, BMD (g/cm2), was measured by dual-energy X-ray absorptiometry in 41 oligomenorrheic ballet dancers aged 17.7±0.2 years (mean ± SEM) and 46 age-matched controls with normal menstrual function. BMD correlated negatively with the duration of oligomenorrhea at weight-bearing and non-weight-bearing sites (femoral neck,r=−0.33,p<0.05; Ward's triangle,r=−0.29,p=0.06; trochanter, r=−0.33,p<0.05; lumbar spine,r=−0.25,p=0.1; skull,r=−0.29,p=0.06; arms,r=−0.32,p<0.05; ribs,r=−0.30,p=0.06). The slopes of the regression of BMD on duration of oligomenorrhea were greater at the proximal femur (trochanter, −0.28±0.13, femoral neck, −0.24±0.11; Ward's triangle, −0.29±0.15) than the skull (−0.15±0.08,p<0.05,p<0.1,p<0.1 respectively). The slopes at the trochanter and femoral neck were also greater than at the ribs (−0.10±0.05; bothp<0.1). In the dancers with oligomenorrhea of less than 40 months duration, BMD was higher than the age-predicted mean at weight-bearing sites (except the lumbar spine), but not at non-weight-bearing sites (femoral neck, 9.1±3.4%; Ward's triangle, 10.0±1.7%; trochanter, 9.4±4.1%, allp<0.05; lumbar spine , −2.1±2.7%, NS; skull, −2.5±2.1%, NS; ribs, −3.0±1.6% NS; arms, −3.9±1.6%;p<0.05). In the dancers with greater than 40 months oligomenorrhea, BMD was no higher than the age predicted mean, at the weight bearing sites, and was lower at non-weight bearing sites (femoral neck, 4.3±2.3%, NS; Ward's triangle, 3.5±3.2%, NS; trochanter, 2.1±2.7%, NS; lumbar spine, −3.8±2.1%, NS; arms, −7.5±0.8%,p<0.05; skull, −6.2±1.8%,p<0.01; ribs, −5.4±1.1%,p<0.0001). In conclusion, weight-bearing exercise is unlikely to offset the deleterious effects of oligomenorrhea. Bone loss appears to occur at all sites but may begin from a higher level at weight-bearing sites and may proceed more rapidly.

Although dual-energy X-ray absorptiometry (DXA) is widely used in clinical research as a means of quantifying body composition, there remains at present little published information that reviews the method's underlying physical basis. Because a clear understanding of DXA physical concepts is integral to appropriate use and interpretation, we present here a three-section review that includes both relevant in vitro and in vivo experimental demonstrations. In the first section we describe the main physical principles on which DXA is based. The section that follows presents a step-by-step analysis of the DXA two-component soft tissue model. In the final section we demonstrate how knowledge of physical concepts can lead to resolution of important methodological concerns, such as the influence of hydration changes on DXA fat estimates. A thorough understanding of DXA physical concepts provides a basis for appropriate interpretation of measurement results and stimulates many new and important research questions.

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (∼0.6 units kg−1 day−1). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA1c was greater in IDDM (5.2 ± 0.7 %) than in NIDDM (2.0 ± 0.4 %, p < 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 ± 1.2 vs 3.77 ± 0.5 kg, p < 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 ± 9.3 %) and fat mass in NIDDM (59.9 ± 8.4 %). The increase in lean mass was greater in IDDM than NIDDM (5.6 ± 1.1 vs 1.4 ± 0.3 kg, p < 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 ± 0.8 vs 2.4 ± 0.5 kg, p = ns) and was predominantly an increase in trunk fat (IDDM: 2.3 ± 0.6 kg, NIDDM: 2.0 ± 0.4 kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 ± 0.05 vs 1.09 ± 0.09, p < 0.01) and then increased in IDDM by 0.32 ± 0.15 (p = 0.07) and in NIDDM by 0.22 ± 0.06 (p < 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.

Are the associations between muscle strength, lean mass, and bone mineral density (BMD) genetically determined? Based on within-pair differences in 56 monozygotic (MZ) and 56 dizygotic (DZ) female twin pairs, mean age 45 yr (range 24-67), BMD was associated with lean mass, independent of fat mass and height (P < 0.05). A 10% increment in femoral neck (FN) BMD was associated with a 15% increment in lean mass (approximately 6 kg). BMD was associated with muscle strength (measured in 35 pairs) before, but not after, adjusting for lean mass. Based on age-adjusted cross-sectional analyses, same-trait correlations (+/- SE) in MZ pairs were double those in DZ pairs: FN BMD (0.62 +/- 0.08, 0.33 +/- 0.12) and lean mass (0.87 +/- 0.03, 0.30 +/- 0.11; all P < 0.001), consistent with a genetic hypothesis. The cross-trait correlation (r) between lean mass and FN BMD in the same individual was 0.43 +/- 0.06. The cross-trait cross-twin correlation between lean mass in one twin and FN BMD in the other was 0.31 +/- 0.07 in MZ pairs, approximately 75% of the cross-trait correlation (r) and 0.19 +/- 0.09 in DZ paris (P < 0.001). After adjusting for height and fat mass, the MZ and DZ cross-trait cross-twin correlations were no different (0.16 +/- 0.08 and 0.13 +/- 0.09, respectively). Therefore, genetic factors account for 60-80% of the individual variances of both FN BMD and lean mass, and > 50% of their covariance. The association between greater muscle mass and greater BMD is likely to be determined by genes regulating size.