Bone Mineral Density Response Research Articles

Using early biomarker data to predict long-term bone mineral density: application of semi-mechanistic bone cycle model on denosumab data.

Osteoporosis is a chronic skeletal disease characterized by low bone strength resulting in increased fracture risk. New treatments for osteoporosis are still an unmet medical need because current available treatments have various limitations. Bone mineral density (BMD) is an important endpoint for evaluating new osteoporosis treatments; however, the BMD response is often slower and less profound than that of bone turnover markers (BTMs). If the relationship between BTMs and BMD can be quantified, the BMD response can be predicted by the changes in BTM after a single dose; therefore, a decision based on BMD changes can be informed early. We have applied a bone cycle model to a phase 2 denosumab dose-ranging study in osteopenic women to quantitatively link serum denosumab pharmacokinetics, BTMs, and lumbar spine (LS) BMD. The data from two phase 3 denosumab studies in patients with low bone mass, FREEDOM and DEFEND, were used for external validation. Both internal and external visual predictive checks demonstrated that the model was capable of predicting LS BMD at the denosumab regimen of 60mg every 6months. It has been demonstrated that the model, in combination with the changes in BTMs observed from a single-dose study in men, is capable of predicting long-term BMD outcomes (e.g., LS BMD response in men after 1year of treatment) in different populations. We propose that this model can be used to inform drug development decisions for osteoporosis treatment early via evaluating LS BMD response when BTM data become available in early trials.

Calcium, Is It Better to Have Less?--Global Health Perspectives.

Appropriate calcium intake is necessary for the accrual and maintenance of bone mass. A significant proportion of the world's population does not have adequate calcium intake, and thus, supplementation plays a key role in maintaining bone homeostasis and other aspects of health. Since a series of reports from the Auckland calcium study and meta-analysis indicated that calcium supplementation was associated with an increased risk for adverse cardiovascular events, concern over the safety of calcium supplementation has grown; however, considerable inconsistencies in the reproducibility were found and questions regarding the study methodologies have been raised. In addition, since the increased adverse cardiovascular events by calcium supplementation were observed in calcium-replete subjects, it should be clarified whether the same risk profile would be observed in countries with low calcium intake. Dietary calcium intake varies widely across the world; cardiovascular event risk factors and outcomes also vary and appear to be the opposite of calcium intake levels. Furthermore, the effects of calcium supplementation were shown to depend on dietary calcium intake, with a better bone mineral density response for low calcium intake subjects compared to that in calcium-replete subjects. Based on these evidences, the risk-benefit ratio of calcium supplement is likely to be different in different region of the world. Therefore, accumulation of evidence to establish population-specific guidelines for calcium supplementation is warranted before extrapolating the results obtained from a limited number of studies to the other people with different age, gender, ethnicity and risk profile across the world.

Daily or Cyclical Teriparatide Treatment in Women With Osteoporosis on no Prior Therapy and Women on Alendronate.

Intermittent 3-month cyclic administration might optimize the anabolic potential of teriparatide (TPTD). To determine whether 3-month cyclical TPTD would produce a similar bone mineral density (BMD) response to daily therapy in treatment naive (Rx-naive) women and to confirm the results in alendronate (ALN)-treated (ALN-Rx) women over 24 months. Subjects participated in a randomized open-label study for 2 years. Osteoporosis clinical research center. A total of 150 postmenopausal women with osteoporosis in two cohorts: 86 Rx-naive and 64 ALN-Rx. Within cohorts, women were randomized to daily TPTD for 24 months or four 3-month TPTD cycles, each followed by 3 months off (12 mo total TPTD). BMD at 24 months. In Rx-naive women, BMD increased in the lumbar spine (LS), total hip (TH), trochanter (Troch), and femoral neck (FN) in daily and cyclic groups (within groups, P < .0002, except cyclic FN, P = .13). Increases were 2-fold greater in daily vs cyclic groups (LS, 8.8 vs 4.8%; TH, 4.0 vs 2.1%; Troch, 5.6 vs 3.1%; and FN, 2.9 vs 1.2%; group differences, all P < .05). In daily vs cyclic groups, radius BMD declined (-4.2 vs -2.1%, respectively; both P < .01; group difference, P = .08) and total bone mineral increased modestly (1.4%, P = .18; vs 1.5%, P = .06; group difference, not significant). In ALN-Rx women, there were no group differences (daily vs cyclic: LS, 7.5 and 6.0%; TH, 3 and 2.5%; Troch, 3.7 and 3.3%; FN, 3 and 1.5%; within groups, P < .003; except cyclic FN, P = .2). In daily and cyclic groups, radius BMD decreased (-0.7% [not significant] and -1.4% [P < .05], respectively), and total bone mineral increased 2.3 and 3% (both P < .001). Cyclic TPTD over 2 years improves BMD similarly to daily treatment in women who remain on ALN, despite only 50% of the TPTD dose. However, there does not appear to be a BMD advantage to cyclic administration in treatment-naive women for up to 24 months.

Elderly men with hypogonadism and osteoporosis. Lack of response to testosterone therapy and the effect of denosumab as an alternative to antiresorptive therapy

Hypogonadal old men have decreased bone mineral density (BMD) and deteriorated trabecular architecture compared with eugonadal men. When the improvement of BMD is achieved with testosterone (To) replacement, there is no data as yet that the rate of fractures is reduced. The objective of this study was to evaluate the BMD in response to denosumab in hypogonadal men with severe osteoporosis but in which To had no effect on BMD at femoral neck, total hip, including the vertebrae.

Electromagnetic field versus circuit weight training on bone mineral density in elderly women.

Background and purposeOsteoporosis is a common skeletal disorder with costly complications and a global health problem and one of the leading causes of morbidity and mortality worldwide. Magnetic field therapy and physical activity have been proven as beneficial interventions for prevention and treatment of osteoporosis. The purpose of this study was to compare the response of bone mineral content and bone mineral density (BMD) in elderly women to either low-frequency low-intensity pulsed magnetic field (LFLIPMF) or circuit weight training (CWT) on short-run basis (after 12 weeks).Patients and methodsThirty elderly women, aged 60–70 years, were randomly assigned into two groups (magnetic field and CWT) (n=15 each group). The session was performed three times per week for magnetic field and CWT groups, for 12 weeks. BMD and bone mineral content of lumbar spine (L2–L4) and femoral neck, trochanter, and Ward’s triangle were evaluated before and after 12 weeks of treatment.ResultsBoth magnetic field and CWT for 12 weeks in elderly women seem to yield beneficial and statistically significant increasing effect on BMD and bone mineral content (P<0.05). But magnetic field seems to have more beneficially and statistically significant effect than does CWT.ConclusionIt is possible to conclude that LFLIPMF and CWT programs are effective modalities in increasing BMD but LFLIPMF is more effective in elderly women.

Response of Bone Mineral Density to Physical Exercises after Thyroidectomy

Introduction: Thyroidectomy could be associated with bone loss because of an endogenous excess of thyroxin, over enthusiastic thyroid replacement therapy following surgery, deregulation of bone resorption as consequence of calcitonin deficiency or some combination of these factors. The aim was to investigate the effect of weight bearing exercises on Improving bone mineral density in post thyroidectomy patients suffering from osteoporosis. Subjects and methods: Thirty osteoporotic patients were assigned randomly into two equal groups; their ages ranged from 20-45 years. The study group received weight bearing exercises program in addition to routine medical treatment. Control group received medical treatment only. Study group received two sessions per week for two successful months. The data were collected before and after the same period of treatment for both groups. Evaluation procedures were carried out to evaluate the bone mineral density using Dual Energy X-ray Absorptiometry. Results: Post treatment both groups showed a variant improvement in bone mineral density, but a significant improvement difference was recorded between the two groups in favor of the study group. Percentage of improvement of bone mineral density in the study group was 10.69%, while it was 2.8% in the control group. Conclusion: Weight bearing exercises were considered to be an effective modality for improving bone mineral density in subjects suffering from osteoporosis following thyroidectomy.

Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.

Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women.

Relationship between pretreatment rate of bone loss and bone density response to once-yearly ZOL: HORIZON-PFT extension study.

Several studies have shown that high bone turnover is associated with greater rates of bone loss and greater bone mineral density (BMD) response to antiresorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss before therapy are associated with greater BMD response to antiresorptive therapy. In the HORIZON-PFT study and its extension, one group of women who were randomized to receive placebo for 3 years (years 1, 2, and 3) were then switched to zoledronic acid (ZOL) 5 mg annually for up to three injections (years 4, 5, and 6, P3Z3 arm) (n = 1223). We measured total hip BMD at baseline, 1, 2, and 3 years on placebo and at 4.5 and 6 years on ZOL. The procollagen type I N-terminal propeptide (PINP) was measured at 3, 4.5, and 6 years. By design, not all subjects were followed for as long as 6 years, so this analysis focused on the results at 4.5 years. Those with the largest loss in total hip BMD on placebo in years 0 to 3 had the largest gain during ZOL (years 3 to 4.5): (r = -0.39, p < 0.0001). The change in total hip BMD in years 0 to 3 on placebo was related to the serum PINP at the end of the 3-year period (r = -0.24, p < 0.0001). The change in total hip BMD on ZOL from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r = 0.26, p < 0.0001). We conclude that BMD response to ZOL is greater in postmenopausal women who had larger loss before treatment. This association may result from higher bone turnover being associated with both greater bone loss on placebo and greater BMD response to ZOL.

A replication study for genome-wide gene expression levels in two layer lines elucidates differentially expressed genes of pathways involved in bone remodeling and immune responsiveness.

The current replication study confirmed significant differences in gene expression profiles of the cerebrum among the two commercial layer lines Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB). Microarray analyses were performed for 30 LSL and another 30 LB laying hens kept in the small group housing system Eurovent German. A total of 14,103 microarray probe sets using customized Affymetrix ChiGene-1_0-st Arrays with 20,399 probe sets were differentially expressed among the two layer lines LSL and LB (FDR adjusted P-value <0.05). An at least 2-fold change in expression levels could be observed for 388 of these probe sets. In LSL, 214 of the 388 probe sets were down- and 174 were up-regulated and vice versa for the LB layer line. Among the 174 up-regulated probe sets in LSL, we identified 51 significantly enriched Gene ontology (GO) terms of the biological process category. A total of 63 enriched GO-terms could be identified for the 214 down-regulated probe sets of the layer line LSL. We identified nine genes significantly differentially expressed between the two layer lines in both microarray experiments. These genes play a crucial role in protection of neuronal cells from oxidative stress, bone mineral density and immune response among the two layer lines LSL and LB. Thus, the different regulation of these genes may significantly contribute to phenotypic trait differences among these layer lines. In conclusion, these novel findings provide a basis for further research to improve animal welfare in laying hens and these layer lines may be of general interest as an animal model.

OP0276 Efficacy of Daily Teriparatide for Two Years on Osteoporosis in Patients with Rheumatoid Arthritis – is IT Appropreate to Combine Daily Teriparatide and Biological Agents?

BackgroundAlthough medication of rheumatoid arthritis (RA) has been improved by early intensive treatment using MTX and biological agents (BIO) for decades, treatment of concomitant disease in RA patients, such as...

OP0260 Denosumab for Patients Receiving Long-Term Glucocorticoids Who do not Have Adequate Response to Bisphosphonate Treatment: A Randomized Controlled Trial

ObjectivesTo evaluate the efficacy of denosumab on bone mineral density (BMD) in patients receiving long-term glucocorticoids who do not have satisfactory response to bisphosphonate treatment.MethodsPatients who were receiving long-term prednisolone...

SAT0480 Effects of A Previous Treatment With18 Months of Teriparatide on the Cortical Bone Mineral Density Response to Three Years of Bisphosphonate Treatment in Severe Osteoporosis

BackgroundThe actual challenge in the management of the severe osteoporosis is to find the best therapeutic strategy to increase bone mineral density (BMD) at the cortical sites, where gains with...

Subgroup variations in bone mineral density response to zoledronic acid after hip fracture.

Minimizing post-fracture bone loss is an important aspect of recovery from hip fracture, and determination of factors that affect bone mineral density (BMD) response to treatment after hip fracture may assist in the development of targeted therapeutic interventions. A post hoc analysis of the HORIZON Recurrent Fracture Trial was done to determine the effect of zoledronic acid (ZOL) on total hip (TH) and femoral neck (FN) BMD in subgroups with low-trauma hip fracture. A total of 2127 patients were randomized (1:1) to yearly infusions of ZOL 5 mg (n = 1065) or placebo (n = 1062) within 90 days of operation for low-trauma hip fracture. The 1486 patients with a baseline and at least one post-baseline BMD assessment at TH or FN (ZOL = 745, placebo = 741) were included in the analyses. Percentage change from baseline in TH and FN BMD was assessed at months 12 and 24 and compared across subgroups of hip fracture patients. Percentage change from baseline in TH and FN BMD at months 12 and 24 was greater (p < 0.05) in ZOL-treated patients compared with placebo in most subgroups. Treatment-by-subgroup interactions (p < 0.05) indicated that a greater effect on BMD was observed for TH BMD at month 12 in females, in patients in the lower tertile body mass index at baseline (≤22.6 kg/m2), and in patients with baseline FN BMD T-score of ≤ –2.5; for FN BMD in patients who received ZOL for >6 weeks post-surgery; and for TH and FN BMD in patients with a history of one or more prior fractures. All interactions were limited to the first 12 months after treatment with none observed for the 24-month comparisons. (Clinical trial registration number NCT00046254.)

Men and women in space: bone loss and kidney stone risk after long‐duration space flight (257.3)

Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long‐duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long‐duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual‐energy X‐ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different.Grant Funding Source: Funded by the NASA Human Research Program.

Modeling and simulation of bone mineral density response from a phase 2 study of ONO‐5334, a new cathepsin K inhibitor, to support dose selection in osteoporosis

ONO-5334, a selective inhibitor of cathepsin K, is a potential new treatment for osteoporosis. The objectives of this modeling study were to (1) develop exposure-response (E-R) models to relate ONO-5334 exposure to bone mineral density (BMD), (2) predict BMD responses to various doses of ONO-5334 for both immediate release tablet (IRT) and sustained release tablet (SRT) formulations where only BMD response after administration of IRT had been studied to date, (3) inform selection of appropriate formulation/dose using simulation for future clinical trials. A population pharmacokinetic (PK) model was developed to simultaneously analyze data for both IRT and SRT. The exposure metrics at steady state were estimated by post hoc Bayesian prediction using the final population PK model. E-R models were developed using dose-ranging data with only IRT from postmenopausal females with osteoporosis. Based on the developed model, lumbar spine and total hip BMD after administration of ONO-5334 SRT as well as IRT were simulated. The simulation results showed that ONO-5334 SRT should provide comparable BMD responses at a lower dose relative to IRT (a finding consistent with the results from a previous population PK-PD modeling study with bone resorption markers).

Men and Women in Space: Bone Loss and Kidney Stone Risk After Long-Duration Spaceflight

Bone loss, a key concern for long-duration space travelers, is typically considered a female issue. The number of women who have flown long-duration space missions is now great enough to allow a quantitative comparison of changes in bone and renal stone risk by sex. Participants were 42 astronauts (33 men and 9 women) on long-duration missions to the International Space Station. Bone mineral density (by dual-energy X-ray absorptiometry) and biochemical markers of bone metabolism (from blood and urine samples) were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. Missions were 49 to 215 days in duration, flown between 2000 and 2012. The bone density response to spaceflight was the same for men and women in both exercise groups. The bone mineral density response to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an advanced resistive exercise device. Biochemical markers of bone formation and resorption responded similarly in male and female astronauts. The response of urinary supersaturation risk to spaceflight was not significantly different between men and women, although risks were typically increased after flight in both groups, and risks were greater in men than in women before and after flight. The responses of men and women to spaceflight with respect to these measures of bone health were not different.

Teriparatide Treatment of Severe Osteoporosis Reduces the Risk of Vertebral Fractures Compared with Standard Care in Routine Clinical Practice

Teriparatide (TPTD) is often used for the treatment of patients with severe osteoporosis, but its effectiveness in this patient group has not been specifically studied. Here, we report upon the results of an observational study involving 323 patients with severe osteoporosis (bone density T-score of -4 or less) who were treated at a specialist osteoporosis clinic with TPTD (n = 217) or standard care (n = 106) over a 5.5-year period. The standard care group did not receive TPTD because they declined to self-inject (59.4%), had a contraindication (7.5%), or were already stabilized on oral bisphosphonates (33%). The two groups were matched for the severity of osteoporosis, fracture risk, and most other clinical variables. The annual percentage change in lumbar spine bone mineral density (BMD) was greater in the TPTD group (8.2 ± 6.0 vs. 5.0 ± 8.4, p = 0.002), but there was no difference in response of hip BMD. During follow-up, 3/217 (1.38%) TPTD-treated patients had new vertebral fractures compared with 7/106 (6.6%) receiving standard care (p = 0.011), but there was no difference between the groups in the rate of nonvertebral fractures (11.1 vs. 8.5%, p = 0.47). Logistic regression analysis adjusting for baseline characteristics showed that the risk of vertebral fractures in TPTD-treated patients was significantly reduced compared with standard care (odds ratio = 0.12, 95% confidence interval 0.03-0.55, p = 0.007). Treatment of severe spinal osteoporosis with TPTD substantially reduces the risk of vertebral fractures compared with standard care and may be the preferred treatment in this patient group.

Single- and Multiple-Dose Randomized Studies of Blosozumab, a Monoclonal Antibody Against Sclerostin, in Healthy Postmenopausal Women

Two clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses (intravenous [iv] and subcutaneous [sc]) of blosozumab in postmenopausal women, including prior/current bisphosphonate (BP) users. In these phase 1, randomized, subject- and investigator-blind, placebo-controlled studies, subjects received escalating doses of blosozumab: single iv doses up to 750 mg, single sc doses of 150 mg, multiple iv doses up to 750 mg every 2 weeks (Q2W) for 8 weeks, multiple sc doses up to 270 mg Q2W for 8 weeks, or placebo. Six subjects were randomized to each dose in the single-dose study (12 to placebo) and up to 12 subjects to each arm in the multiple-dose study. Blosozumab was well tolerated with no safety concerns identified after single or multiple administrations up to 750 mg. Dose-dependent responses were observed in sclerostin, N-terminal propeptide of procollagen type 1, bone-specific alkaline phosphatase, osteocalcin, C-terminal fragment of type 1 collagen, and bone mineral density (BMD) after single and multiple (up to 5) administrations of blosozumab. There was up to a 3.41% (p=0.002) and up to a 7.71% (p<0.001) change from baseline in lumbar spine BMD at day 85 after single or multiple administrations of blosozumab, respectively. Prior BP use did not appear to have a clear impact on the effects of single doses of blosozumab when considering bone biomarker and BMD responses. Antibodies to blosozumab were detected by a screening assay, but no patterns with regard to dose or route of administration and no clear impact on blosozumab exposure or PD responses were identified. In summary, blosozumab was well tolerated and exhibited anabolic effects on bone. These findings support further investigation of blosozumab as a potential anabolic therapy for osteoporosis.

Changes in thigh muscle volume predict bone mineral density response to lifestyle therapy in frail, obese older adults

We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD. Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise. One hundred seven obese older adults were randomized to control, diet, exercise, and diet-exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay. Thigh muscle volume decreased in the diet group (-6.2 ± 4.8 %) and increased in the exercise group (2.7 ± 3.1 %), while it was not significantly different from the control in the diet-exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23 ± 20 %; 25 ± 19 %) and diet-exercise group (20 ± 19 %; 20.6 ± 27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD (r = 0.55, P = <0.001) and were an independent predictor of changes in hip BMD (β = 0.12, P = 0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no correlations between BMD changes and knee strength, 1-RM, and sclerostin changes. Changes in thigh muscle volume predict hip BMD changes in obese older patients undergoing lifestyle therapy. The effect of exercise in attenuating thigh muscle loss when added to diet may in part account for the reduction in weight loss-induced bone loss in the diet-exercise group.

Regional, but not total, body composition changes in overweight and obese adults consuming a higher protein, energy-restricted diet are sex specific

Secondary analyses of data from 2 studies were used to assess the effects of protein intake and sex on diet-induced changes in body composition. The primary hypothesis was that the changes of body composition via energy restriction (ie, lean body mass [LBM], fat mass [FM], and bone) would be sex and diet specific. For 12 weeks, 43 male (study 1) and 45 female (study 2) overweight and obese adults consumed an energy-deficit diet (750 kcal/d less than energy needs) containing either 0.8 (normal protein [NP], 21 men and 23 women) or 1.4 g protein∙kg−1∙d−1 (high protein [HP], 22 men and 22 women). Body composition measurements were performed at preintervention and postintervention. Over time, all research participants lost weight, LBM, and FM. Independent of protein intake, the men lost more LBM in the trunk (−0.9 vs −0.5 kg) and less in the legs (−1.5 vs −1.1 kg) compared with the women (P < .05). Independent of sex, the HP group lost less LBM in the trunk and legs than the NP group. These sex and protein intake responses resulted in the NP men losing the most LBM in the legs and the NP women losing the most LBM in the trunk. Over time, men lost more FM (−5.0 vs −3.9 kg) from the trunk and less from legs (−1.7 vs −2.1 kg) than women (P < .05), which resulted in a greater decrease of the android-to-gynoid fat ratio for the men. Protein intake did not influence these sex-specific responses or have any independent effects on changes in FM. In addition, protein intake did not influence bone mineral density responses over time; bone mineral density was reduced in women, but not in men. These findings indicate that higher protein intake during weight loss promotes the retention of LBM in both the trunk and legs despite the sex-specific changes in these body regions.