Bone Loss In Adults Research Articles

Calorie restriction in mice impairs cortical but not trabecular peak bone mass by suppressing bone remodeling.

Calorie restriction (CR) can lead to weight loss and decreased substrate availability for bone cells. Ultimately, this can lead to impaired peak bone acquisition in children and adolescence and bone loss in adults. But the mechanisms that drive diet-induced bone loss in humans are not well characterized. To explore those in greater detail, we examined the impact of 30% CR for 4 and 8wk in both male and female 8-wk-old C57BL/6J mice. Body composition, areal bone mineral density (aBMD), skeletal microarchitecture by micro-CT, histomorphometric parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. After 8wk, CR mice lost weight and exhibited lower femoral and whole-body aBMD vs ad libitum (AL) mice. By micro-CT, CR mice had lower cortical bone area fraction vs AL mice, but males had preserved trabecular bone parameters and females showed increased bone volume fraction compared to AL mice. Histomorphometric analysis revealed that CR mice had a profound suppression in trabecular as well as endocortical and periosteal bone formation in addition to reduced bone resorption compared to AL mice. Bone marrow adipose tissue was significantly increased in CR mice. In vitro, the pace of adipogenesis in bone marrow stem cells was greatly accelerated with higher markers of adipocyte differentiation and more oil red O staining, whereas osteogenic differentiation was reduced. qRT-PCR and western blotting suggested that the expression of Wnt16 and the canonical β-catenin pathway was compromised during CR. In sum, CR causes impaired peak cortical bone mass due to a profound suppression in bone remodeling. The increase in marrow adipocytes in vitro and in vivo is related to both progenitor recruitment and adipogenesis in the face of nutrient insufficiency. Long-term CR may lead to lower bone mass principally in the cortical envelope, possibly due to impaired Wnt signaling.

Abstract P180: Hypertension-linked Immune Activation Regulates Osteoclastogenesis

Osteoporosis is an age-related disease affecting 18% of adults. Hypertension is associated with increased risk for fragility fracture and accelerated bone loss in adults. We hypothesized that experimental hypertension would induce osteoporosis and examined the mechanisms involved. We used two preclinical models in 12-week-old male C57Bl/6J mice: angiotensin (ang) II infusion (490 ng/kg/min) and deoxycorticosterone acetate (DOCA)-salt. After 6 weeks of ang II or 3 weeks of DOCA-salt, the left femur and sixth lumbar vertebral body were studied. Mechanical testing showed that ang II reduced femoral ultimate strength (170.7±4.794 vs 157.3±3.670 MPa, p=0.0325; 154.1±7.403 vs. 119.9±4.375 MPa, p=0.0026) and peak moment (39.09±1.660 vs. 32.77±0.9380 Newton millimeters (Nmm), p=0.0018; 29.15±1.291 vs 19.58±1.308 Nmm, p=0.0004) with cortical and trabecular bone loss compared to controls. μCT showed that hypertension reduced vertebral body bone volume fraction (30.1±1.41 vs 25.1±0.992 %, p=0.0068; 25.9±2.03 vs 18.5±1.29 %, p=0.0119) and trabecular thickness (62±1.6 vs 57±1.4 μm, p=0.0105; 60±2.1 vs 51 ±1.6 μm, p=0.0069). Flow cytometry of bone marrow from ang II-treated mice revealed that CD4+ T cells and γδ T cells produce increased IL-17A which is known to induce osteoclastogenesis. Colony stimulating factor-1 (CSF1) is also known to stimulate osteoclast formation. Using in situ hybridization, we observed increased CSF1 mRNA in endothelial cells (ECs) of transcortical arterioles of hypertensive mice. Subsequent studies of cultured bone marrow derived ECs showed that CSF1 mRNA expression increased with 0% and 10% compared to 5% stretch. 5% stretch treated with endothelial nitric oxide synthase inhibitor, L-NAME, increased expression comparable to 0% and 10%, indicating that nitric oxide inhibits CSF1 production. Thus, T-cell activation and nitric oxide-dependent EC dysfunction in hypertension may skew the bone marrow to favor osteoclastogenesis, leading to bone loss. Understanding this mechanism will elucidate novel pharmacological targets to mitigate hypertension-induced bone loss.

Exercise effects on glucocorticoid-induced bone loss in adults: a systematic review and meta-analysis.

Due to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy. A systematic literature search of five electronic databases included controlled trials with a duration of >6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN). We identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI -0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I 2 = 71%, FN-BMD I 2 = 78%) between the study results. Although more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP. PROSPERO: CRD42022308155.

High-Fat Diet Increases Bone Loss by Inducing Ferroptosis in Osteoblasts.

Current research suggests that chronic high-fat dietary intake can lead to bone loss in adults; however, the mechanism by which high-fat diets affect the development of osteoporosis in individuals is unclear. As high-fat diets are strongly associated with ferroptosis, whether ferroptosis mediates high-fat diet-induced bone loss was the focus of our current study. By dividing the mice into a high-fat diet group, a high-fat diet + ferroptosis inhibitor group and a normal chow group, mice in the high-fat group were given a high-fat diet for 12 weeks. The mice in the high-fat diet + ferroptosis inhibitor group were given 1 mg/kg Fer-1 per day intraperitoneally at the start of the high-fat diet. Microscopic CT scans, histological tests, and biochemical indicators of ferroptosis were performed on bone tissue from all three groups at the end of the modelling period. Mc3t3-E1 cells were also used in vitro and divided into three groups: high-fat medium group, high-fat medium+ferroptosis inhibitor group, and control group. After 24 hours of incubation in high-fat medium, Mc3t3-E1 cells were assayed for ferroptosis marker proteins and biochemical parameters, and osteogenesis induction was performed simultaneously. Cellular alkaline phosphatase content and expression of osteogenesis-related proteins were measured at day 7 of osteogenesis induction. The results showed that a high-fat diet led to the development of femoral bone loss in mice and that this process could be inhibited by ferroptosis inhibitors. The high-fat diet mainly affected the number of osteoblasts produced in the bone marrow cavity. The high-fat environment in vitro inhibited osteoblast proliferation and osteogenic differentiation, and significant changes in ferroptosis-related biochemical parameters were observed. These findings have implications for the future clinical treatment of bone loss caused by high-fat diets.

Safety and Tolerability of SBD111 an Optimized Probiotic/Prebiotic Medical Food Combination Designed for the Dietary Management of Age-Related Bone Loss in Adults.

ObjectivesTo determine the effect of a daily administration of 6.1 × 1010 CFU/d of SBD111 (an optimized probiotic/prebiotic combination) on safety and tolerability in adults in a randomized trial. MethodsParticipants (n = 32) were randomized to either SBD111 or placebo. The primary outcomes were the number, frequency and severity of adverse Gastrointestinal (GI) symptoms over 28-d. Secondary outcomes were the number and severity of all adverse events (AEs). Stool samples were collected at baseline and after 28-d to determine the impact of SBD111 on gut microbial engraftment, diversity and function using shotgun metagenomics. Groups were compared using Incidence Rate Ratios (negative binomial regression), Odds Ratios (logistic regression) and 95%CI (P< 0.05) using intention-to-treat approach. ResultsAt baseline, the mean age was 45(SD:18)y in SBD111 users (n = 5M, 10F) vs 42(SD:14)y in placebo users (n = 5M, 12F). The two groups did not significantly differ in age, BMI, blood pressure and screening labs. After 28-d, the presence of GI symptoms tended to be higher with SBD111 use vs placebo (P = 0.08). The total number, frequency/severity of GI symptoms did not significantly differ between groups and only 1 person withdrew from the placebo group due to side effects. The number of AEs possibly related to the study were significantly higher with SBD111 use vs placebo (P = 0.05), there were no significant differences in the mean number or severity of AEs. The majority of reported AEs were mild, some were moderate, but none were severe. There were no significant differences in Shannon diversity/microbial richness between the two groups at baseline or after 28-d. After 28-d, participants receiving SBD111 but not placebo showed a significant enrichment in metabolic pathways of menaquinone (vitamin K2) production including the superpathway of menaquinol-10. Fragment recruitment analysis identified the genomic signal of the strains comprising SBD111 after 28-d of SBD111 use, but not placebo. SBD111 strains were undetectable at baseline in either group. ConclusionsThe relatively low frequency and mild severity of GI symptoms and AEs suggests that SBD111 at the level tested is safe for human consumption and that SBD111 microbes are able to pass through the intestinal tract, be identified in stool and enrich microbial gene pathways related to bone health. Funding SourcesSolarea Bio Inc.

Association between macronutrients intake distribution and bone mineral density

Although it is well known dietary factors are closely correlated with bone health, the association between macronutrients intake distribution and bone mineral density (BMD) is still unclear. The aims of this study were to investigate how macronutrients distribution was correlated with BMD, and to evaluate how the substitution between macronutrients could be associated with BMD. We conducted a cross-sectional study based on data from National Health and Nutrition Examination Survey. Dietary recall method was used to assessed the intake of macronutrients. Macronutrient intake distribution including carbohydrate, protein and fat was calculated as percentages of energy intake from total energy. BMD was converted to T-score and low BMD was defined as T-score less than-1.0. The association between the percentages of energy intake from carbohydrate, protein and fat with T-score and risk of low BMD was evaluated using multivariate regression models. Isocaloric substitution analysis was conducted using the multivariate nutrient density method. Data form 4447 adults aged 20 years and older who underwent BMD examination were included in this study. Higher percentage of energy intake from carbohydrate was associated with lower T-score (-0.03 [95%CI,-0.05 to-0.01]; P=0.001) and higher risk of low BMD (1.05 [95%CI, 1.02-1.08]; P=0.003), while higher percentage of energy intake from protein was associated with higher T-score (0.05 [95%CI, 0.01-0.08]; P=0.009) and lower odds of low BMD (0.92 [95%CI, 0.87-0.98]; P=0.007). The percentage of energy intake from fat seemed to be positively correlated with T-score, but the correlation became insignificant after adjusting for metabolism related confounders. Isocaloric substitution analysis showed that only the substitution between carbohydrate and protein was significantly and independently associated with T-score (-0.05 [95%CI,-0.08 to-0.01]; P=0.01) and the risk of low BMD (1.08 [95%CI, 1.02-1.15]; P=0.008). Based on the results from this study, we hypothesized that a high-protein diet coupled with low carbohydrate intake would be beneficiary for prevention of bone loss in adults. However, randomized clinical trials or longitudinal studies are needed to further assessed our findings.

Associations of Sex Hormone-binding Globulin with Bone Mineral Density Among US Adults, NHANES 2013-2016.

BackgroundBone metabolism can be influenced by sex steroid hormones. However, the relationship between sex steroid hormones and bone mineral density (BMD) remains inconsistent. Our study explored existing evidence of the association between sex hormones, blood glucose and BMD.MethodsWe conducted a cross-sectional study of 6434 participants aged 18–80 years in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 to assess the association between SHBG and BMD. The multivariable linear regression models were performed to evaluate the associations between testosterone, estrogen, sex hormone-binding globulin (SHBG) and BMD.ResultsOn adjustment for traditional risk factors (age, BMI, ALB, ALK, ASP, calcium, cholesterol, potassium, sodium, total protein, uric acid), SHBG could be regarded as an independent predictor for BMD, while fasting blood glucose did not. SHBG levels were significant associated with BMD in the multivariate model; however, it will be a different effect between the genders. On comparative analysis, high level SHBG was predictive of lumbar BMD irrespective of other two sex steroid hormones.ConclusionThis study indicated that SHBG may improve the predictive value for bone loss in adults.

Collagen-binding peptide reverses bone loss in a mouse model of cerebral palsy based on clinical databases.

Individuals with cerebral palsy (CP) experience bone loss due to impaired weight bearing. Despite serious complications, there is no standard medication. To develop a new pharmacological agent, we performed a series of studies. The primary aim was to develop an animal model of CP to use our target medication based on transcriptome analysis of individuals with CP. The secondary aim was to show the therapeutic capability of collagen-binding peptide (CBP) in reversing bone loss in the CP mouse model. A total of 119 people with CP and 13 healthy adults participated in the study and 140 mice were used for the behavioral analysis and discovery of therapeutic effects in the preclinical study. The mouse model of CP was induced by hypoxic-ischemic brain injury. Inclusion and exclusion criteria were established for CBP medication in the CP mouse model with bone loss. On the basis of clinical outcomes showing insufficient mechanical loading from non-ambulatory function and that underweight mainly affects bone loss in adults with CP, we developed a mouse model of CP with bone loss. Injury severity and body weight mainly affected bone loss in the CP mouse model. Transcriptome analysis showed SPP1 expression downregulated in adults with CP who showed lower bone density than healthy controls. Therefore, a synthesized CBP was administered to the mouse model. Trabecular thickness, total collagen and bone turnover activity increased with CBP treatment as compared with the saline control. Immunohistochemistry showed increased immunoreactivity of runt-related transcription factor 2 and osteocalcin, so the CBP participated in osteoblast differentiation. This study can provide a scientific basis for a promising translational approach for developing new anabolic CBP medication to treat bone loss in individuals with CP.

Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis.

Cell-free based therapy is an effective strategy in regenerative medicine as it avoids controversial issues, such as immunomodulation and stability. Recently, exosomes have been explored as a favorable substitution for stem cell therapy as they exhibit multiple advantages, such as the ability to be endocytosed and innate biocompatibility. This study aimed to investigate the effects of stem cells from human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exo) on bone marrow stromal cells (BMSCs) osteogenesis and bone recovery. SHED-Exo were isolated, characterized, and applied to the bone loss area caused by periodontitis in a mouse model. We found that the injection of SHED-Exo restored bone loss to the same extent as original stem cells. Without affecting BMSCs proliferation, SHED-Exo mildly inhibited apoptosis. Moreover, SHED-Exo specifically promoted BMSCs osteogenesis and inhibited adipogenesis compared with SHED-derived conditioned medium. The expression of osteogenic marker genes, alkaline phosphatase activity, and Alizarin Red S staining of BMSCs was significantly increased by co-culturing with SHED-Exo. Moreover, Western blot analysis showed that Runx2, a key transcriptional factor in osteogenic differentiation, and p-Smad5 were upregulated upon SHED-Exo stimulation. Expression of the adipogenic marker PPARγ and the amount of lipid droplets decreased when exosomes were present. Low doses of exosomes inhibited the expression of the inflammatory cytokines IL-6 and TNF-α. In conclusion, SHED-Exo directly promoted BMSCs osteogenesis, differentiation, and bone formation. Therefore, exosomes have the potential to be utilized in the treatment of periodontitis and other bone diseases.

Informed decision making for the elderly patient with newly diagnosed coeliac disease.

To The Editor We thank Dr. W.Shanahan and Dr. J.Shanahan for their interest in our study (1). In their letter, they have raised a few important points that we wish to clarify. Firstly, they implied that we had a lack of appreciation for the recognition and prevention of bone-related morbidity in elderly Coeliac Disease (CD) patients. We respectfully disagree with their statement; throughout our paper, we repeatedly highlighted the importance of recognising such complications in this group of patients. Moreover, we reported that elderly CD patients had a significantly higher risk of osteopenia/osteoporosis compared to younger patients. In our practice, we routinely measure serum vitamin D, alkaline phosphatase and calcium levels for all CD patients and refer those older than 55 years or with known osteoporotic risk factors for bone density scans following the British Society of Gastroenterology guidelines. (2) A single centre audit, while valuable in improving local practices, should not be used to generalise poor adherence to national guidelines. Secondly, we agree that CD is associated with an increased risk of osteoporosis and fractures. However, GFD adherence rarely reverses bone loss in adults. This is particularly evident in elderly patients with long-term exposure to gluten and established bone disease at the time of diagnosis (3, 4). In our study, 57% of the osteopenic/osteoporotic elderly patients with CD were completely asymptomatic. Therefore, without strong evidence from randomised controlled trials or large prospective studies showing a clear benefit from adhering to a strict GFD over nutritional supplementation, only in this age group, we have to raise the question whether it is worthwhile breaking lifetime dietary habits in asymptomatic elderly patients. Finally, should we be diagnosing Coeliac Disease in the elderly? The answer is probably yes. However, the majority of these elderley patients show little to no gastrointestinal symptoms and are often referred due to cancer or metabolic pathways with unexplained anaemia and bone loss. Hence, the diagnosis of CD may come as a shock to them. We feel that empowering elderly patients to adopt a GFD on an individual level based on the presence or absence of symptoms might be appropriate. Nonetheless, future research is needed to evaluate the alternatives to GFD and the other long-term risks of CD, such as malignancy and anaemia, before accepting such an approach.

Sclerostin and bone metabolism markers in hyperthyroidism before treatment and interrelations between them.

Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with Wnt signal pathway and it has been reported that increased thyroid hormones in hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk of bone fractures by stimulating the bone loss in adults. The aim of this study was to examine the sclerostin serum levels, the relation between sclerostin and thyroid hormones as well as the biochemical markers of the bone metabolism in patients with hyperthyroidism (including multinodular goiter and Graves' disease), whose treatments have not started yet. No difference was found in the serum sclerostin levels between the hyperthyroidism group (n=24) and the control group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary phosphorus excretion were found to be higher in the hyperthyroid group than in the control group (p<0.001, p=0.009). A positive correlation was determined between the sclerostin and bone alkaline phosphatase levels (p<0.001); a negative correlation between the osteocalcin and thyroid stimulating hormone (TSH) (p<0.05); a positive correlation between the osteocalcin and thyroid hormones (FT3,FT4) (p<0.001); and a positive correlation between the deoxypyridinoline and hydroxyproline (p<0.001). No correlation was determined between sclerostin and TSH,FT3,FT4 (p>0.05). Therefore, we consider that a long-term study that covers the pre-post treatment stages of hyperthyroidism, including both the destruction and construction of the skeleton would be more enlightening. Moreover, the assessment of the synthesis of sclerostin in the bone tissue and in the serum level might show differences.

Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial.

This study aimed to determine the effect of fish oil on bone mineral density (BMD). There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD. This randomized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on bone loss in adults. The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD. In a multicentre, double-blind randomized controlled trial (RCT) (ACTRN 12607000415404), 202 Australian participants aged ≥40 with knee osteoarthritis (mean age, 61.0 ± 10.0years; 49% female) were randomized to receive either high dose (4.5g eicosapentaenoic acid and docosahexaenoic acid daily) or low dose (0.45g/day) omega-3 fish oil for 2years. BMD was assessed at baseline and 2years by dual energy X-ray absorptiometry. In subjects with baseline and 2-year assessments, mean standardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169mg/cm(2), respectively, for the lumbar spine and was 1035 ± 165 and 1017 ± 174mg/cm(2), respectively, for the femoral neck. There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses (lumbar spine 3.7, 95% confidence interval (CI) -7.9 to 15.3mg/cm(2) and femoral neck -5.5, 95% CI -14.9 to 3.9mg/cm(2)). The findings did not change with additional adjustments of age, gender, study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants (≥55years at the baseline) (all P ≥ 0.25). Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group. There were no serious adverse events related to the intervention. A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis.

Chemotherapy- and irradiation-induced bone loss in adults with solid tumors.

It is estimated that bone loss occurs in 70 % of all patients dying from cancer, causing a significant disease burden in cancer patients. Bone loss is caused by cancer itself and its metastases, but also by cancer therapies. Of the cancer therapy-induced bone loss, hormone therapies are best known for their bone damaging abilities. However, chemo- and radiotherapy may result in bone loss too. In this review, direct and indirect effects of various chemotherapies (such as methotrexate, imatinib, and taxanes) that cause bone loss are discussed. Furthermore, we discuss bone loss caused by radiotherapy and radionuclides, of which the latter may be reduced with the introduction of the alpha-emitter Radium-223. Finally, agents preventing chemotherapy- or radiotherapy-induced bone loss, in particular denosumab and bisphosphonates, are being reviewed for their efficacy in preventing chemotherapy- and irradiation-induced bone loss in cancer patients.

Bone mass and bone quality are altered by hypoactivity in the chicken.

Disuse induces a rapid bone loss in adults; sedentarity is now recognized as a risk factor for osteoporosis. Hypoactivity or confinement also decrease bone mass in adults but their effects are largely unknown and only few animal models have been described. We have used 10 chickens of the rapidly growing strain 857K bred in a large enclosure (FREE group); 10 others were confined in small cages with little space to move around (HYPO group). They were sacrificed at 53 days and femurs and tibias were evaluated by texture analysis, dual energy X-ray densitometry, microcomputed tomography (microCT) and histomorphometry. Hypoactivity had no effect on the length and diameter of the bones. Bone mineral density (BMD), microCT (trabecular bone volume and trabecular microarchitecture) and texture analysis were always found significantly reduced in the animals of the HYPO group. BMD was reduced at both femur and tibia diaphysises; BMD of the metaphysis was significantly reduced in the femur but not in the tibia. An increase in osteoid volume and surfaces was noted in the HYPO group. However, there was no alteration of the mineral phase as the osteoid thickness did not differ from control animals. Bone loss was much more pronounced at the lower femur metaphysis than at the upper metaphysis of the tibia. At the tibia, only microarchitectural changes of trabecular bone could be evidenced. The confined chicken represents a new method for the study of hypodynamia since these animals do not have surgical lesions.

Bisphosphonate therapy in pediatric patients.

Although for many decades bisphosphonates were used for adult bone loss, bisphosphonate administration in pediatric patients is new and was initiated in the past 15-year. The indications for pediatric bisphosphonates was extended to childhood malignancies with bone involvement, after additional effects were unveiled for bisphosphonates with recent research. In this article we review childhood bone loss and conditions with bone involvement in which bisphosphonate therapy have been used. We also review mechanisms of action of bisphosphonates, and present indications of bisphosphonate therapy in pediatric patients based on results of clinical trials.

Intermittent Zoledronic Acid Prevents Bone Loss in Adults after Allogeneic Hematopoietic Cell Transplantation

Bone mineral density (BMD) loss is common in survivors of allogeneic hematopoietic cell transplantation (alloHCT). We performed a multicenter, phase II, randomized open-label trial of intravenous zoledronic acid (ZA) to prevent BMD loss in adult recipients of alloHCT with osteopenia before HCT. The treatment group received ZA 4 mg intravenously within 28 days pre-HCT and at 3 and 6 months after HCT. Both treatment and control groups received calcium carbonate and vitamin D supplements. Of 61 patients, 32 were randomized to the ZA cohort and 29 to the control cohorts. More patients in the ZA group had an HCT comorbidity index high-risk score of ≥3 (50% versus 21%, P < .01). Baseline BMD, T-scores, serum osteocalcin, bone alkaline phosphatase, and urine N-telopeptide (UNTX) levels were similar in both cohorts. Thirty patients were evaluable for outcomes (11 from the treatment and 19 from the control group). At 12 months, subjects in the treatment group had an improvement in BMD at the femoral neck (mean change, .018 for ZA group versus −.054 for controls; P = .04) and a significant decline in levels of UNTX (−56 for ZA group versus −9 for control; P = .04) compared with baseline. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw or renal impairment. Lower survival observed in the ZA cohort was likely related to baseline imbalance in HCT-CI scores. Intermittent ZA is effective in preserving long-term bone health in adult alloHCT recipients at risk for osteoporosis.

Bone loss in adults with cystic fibrosis: Prevalence, associated factors, and usefulness of biological markers

Background Osteoporosis is a common complication of cystic fibrosis. Objective To determine the prevalence of osteopenia and osteoporosis in adults with cystic fibrosis and to look for factors associated with low bone mineral density (BMD) values. Methods During this prospective 2-year study, we collected clinical data (history, body mass index, and treatments) and laboratory data (nutritional and hormonal status, markers for inflammation and bone turnover, and calcium and phosphate levels). Lung function tests and a 6-meter walking test were performed. BMD was measured at the spine, total hip, and femoral neck. Results We included 55 patients (31 women) with a mean age of 31.9 years; 14 were homozygous and 25 heterozygous for the deltaF508 mutation and 20 (36%) had a history of fractures. BMD values indicated osteopenia in 32 (58.2%) patients and osteoporosis in 11 (20%) patients at one or more measurement sites. At all three sites, BMD values correlated with the body mass index, forced vital capacity as % predicted, and forced expiratory volume in 1 s as % predicted; at the femoral neck and total hip, BMD values correlated with the 6-meter walking test result and grip strength. Conclusion BMD was low in 78.2% of adults with cystic fibrosis. Three factors reflecting lung disease severity were associated with low BMD values, namely, respiratory function, physical function (walking test and grip strength), and nutritional status.

Effects of Risedronate and Low-Dose Transdermal Testosterone on Bone Mineral Density in Women with Anorexia Nervosa: A Randomized, Placebo-Controlled Study

Anorexia nervosa is complicated by severe bone loss and clinical fractures. Mechanisms underlying bone loss in adults with anorexia nervosa include increased bone resorption and decreased formation. Estrogen administration has not been shown to prevent bone loss in this population, and to date, there are no approved, effective therapies for this comorbidity. To determine whether antiresorptive therapy with a bisphosphonate alone or in combination with low-dose transdermal testosterone replacement would increase bone mineral density (BMD) in women with anorexia nervosa. We conducted a12-month, randomized, placebo-controlled study at a clinical research center. Participants included 77 ambulatory women with anorexia nervosa. Subjects were randomized to risedronate 35 mg weekly, low-dose transdermal testosterone replacement therapy, combination therapy or double placebo. BMD at the spine (primary endpoint), hip, and radius and body composition were measured by dual-energy x-ray absorptiometry. Risedronate increased posteroanterior spine BMD 3%, lateral spine BMD 4%, and hip BMD 2% in women with anorexia nervosa compared with placebo in a 12-month clinical trial. Testosterone administration did not improve BMD but increased lean body mass. There were few side effects associated with either therapy. Risedronate administration for 1 yr increased spinal BMD, the primary site of bone loss in women with anorexia nervosa. Low-dose testosterone did not change BMD but increased lean body mass.

Disorders of ovarian function in childhood and adolescence: evolving needs of the growing child. An endocrine perspective

Over the past 15 years there have been changes in the care of children and adolescents paralleling increased longevity of those with chronic illnesses and increased survival after childhood cancer and organ transplantation. A broad understanding of holistic management and long-term risks is required. Optimisation of pubertal progress and normalisation of bone and hormonal health by the end of puberty will reduce the impact of later adult bone loss in chronic disease conditions. Psychosocial issues related to both precocious and delayed puberty can have profound effects on family function.

Variation in lumbar spine bone mineral content by age and gender in apparently healthy Indians

The aim of this study was to assess variation in bone mass from childhood through later age and to examine bone health status of Indian males and females. Lumbar spine (LS) bone mineral content (BMC) was measured by dual energy X-ray absorptiometry of lumbar vertebrae (L1-L4) in 683 males and 858 females (5-70 years) from Pune, India and apparent bone mineral density (BMAD) was calculated. A cubic regression model was fitted to describe the change in bone mineral content (BMC) with age in males and females separately. Regression analysis revealed that peak LS BMC was achieved around 26 years (63.6 +/- 11.0 g) for males and 30 years (54.1 +/- 11.6 g) for females. After 50 years of age, BMC showed an average annual decrease of 2.7% in males and 4.1% in females. Males had 11-15% higher mean BMAD than females after 50 years of age. T scores of 19% males and 28% females above 50 years, were less than -2.5 and T scores of 36% males and 43% females were between -1.0 and -2.5 when compared with the Lunar reference database. Low peak bone mass at a young age and higher bone loss in adults are alarming features of apparently healthy Indians.