Changes In Femoral Neck Research Articles

7740 Adult-Onset Hypophosphatasia Presenting As Low Alkaline Phosphatase Level Following Denosumab Use For Osteoporosis

Abstract Disclosure: J. Ocampo Mascaro: None. P. Wax: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding. Background: Hypophosphatasia (HPP) is a genetic disease characterized by low activity of the tissue non-specific alkaline phosphatase. It has a broad range of clinical phenotypes, with adults usually presenting with an incidental low alkaline phosphatase (ALP) finding. Differentiating this from other causes of low ALP is challenging, especially when treating osteoporosis, as antiresorptive therapy such as denosumab and bisphosphonates may cause low ALP and carry the potential of increasing risk of atypical femoral fractures in patients with undiagnosed HPP. Clinical Case: A 64-year-old woman with history of nephrolithiasis, hypercalciuria, and osteoporosis (screening DXA lowest T-score -3.3 in femoral neck (FN)) but no prior fractures or dental issues was seen in clinic. Initial bloodwork showed normal range calcium, 25-OH vitamin D, and intact PTH. Pre-treatment ALP was 42 IU/L (N 39-117). Work up for secondary causes of osteoporosis was negative. Three yearly doses of IV zoledronic acid resulted in +4.2% BMD increase in lumbar spine (LS) but no changes in FN. She had no side effects but was found to have a decrease in ALP to 33 IU/L. This normalized back to 42 IU/L during a three-year drug holiday. Follow up DXA noted significant decline in BMD, hence denosumab was initiated. ALP decreased back to the 30-35 IU/L range. Fasting Vitamin B6 level (off B6 supplements for 1 week) was 23.4 ng/ml (N 2.1-21). Urine phosphoethanolamine was mildly elevated at 5 mmol/mol creatinine (N ≤4). Genetic testing evidenced a pathogenic ALPL variant (Exon 6, c.575T>C (p.Met192Thr), heterozygous) compatible with HPP. She had tolerated three doses of denosumab by then with BMD improvement of 5.0% in LS but no changes in FN and no atypical femoral fracture. Denosumab was stopped. Abaloparatide was started for osteoporosis with close monitoring for worsening hypercalciuria. Conclusion: This case demonstrates that adult HPP patients may present with subtle findings and lower range of normal ALP and may tolerate short courses of antiresorptive agents. There is a need for better screening and diagnostic criteria for adult HPP patients whose ALP levels may not be initially low before initiating antiresorptive drugs for osteoporosis. The risk of adverse effects from therapy will likely vary significantly based on the clinical severity/presentation of HPP as some adults with lower ALP ranges might be more susceptible to developing atypical femur fractures (1). Balancing atypical femur fracture risk with the benefits of antiresorptive treatment in decreasing risk of osteoporotic fractures highlights the need for better risk stratification to prevent undertreatment of osteoporosis. Reference: 1. Warren AM, Ebeling PR, Grill V, Seeman E, Sztal-Mazer S. Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia. Endocrinol Diabetes Metab Case Rep. 2021 Sep 1;2021:21-0096. Presentation: 6/2/2024

Shift in Calcium From Peripheral Bone to Axial Bone After Tumor Resection in Patients With Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear. This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients. We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study. In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius. Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients.

Comparison of full thread compression cannulated screw and partial thread cannulated screw in treatment of femoral neck fracture

To compare the effectiveness of full thread compression cannulated screw and partial thread cannulated screw in the treatment of femoral neck fracture. A retrospective analysis was made on 152 patients with femoral neck fractures, who met the selection criteria, between April 2013 and February 2021. The fractures were fixed with the full thread compression cannulated screws in 74 cases (trial group) and the partial thread cannulated screws in 78 cases (control group). There was no significant difference in general data such as age, gender, body mass index, cause of injury, time from injury to operation, and the side, Garden typing, Pauwels typing of fracture between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, follow-up time, and Harris score were recorded in both groups. X-ray films were performed to evaluate the quality of fracture reduction and bone healing, the changes of neck-shaft angle, the changes of femoral neck, as well as the occurrence of internal fixation failure, screw back-out, and osteonecrosis of the femoral head. There was no significant difference in operation time and hospital stay between the two groups (P>0.05). However, the intraoperative blood loss in the trial group was significantly lower than that in the control group (P<0.05). Patients in both groups were followed up, with the follow-up time of (24.11±4.04) months in the trial group and (24.10±4.42) months in the control group, and the difference was not significant (P>0.05). Postoperative X-ray films showed that there was no significant difference in fracture reduction grading between the two groups (P>0.05). Six cases in the trial group developed bone nonunion and 7 cases in the control group, the fractures of the other patients healed, and the healing time was significantly shorter in the trial group than in the control group (P<0.05). There was no significant difference in the incidence of bone nonunion between the two groups (P>0.05). During follow-up, 2 cases in the trial group and 5 cases in the control group had osteonecrosis of the femoral head, the difference was not significant (P>0.05), and the patients with osteonecrosis of the femoral head were treated with secondary operation. The screw back-out occurred in 3 cases of the trial group and in 9 cases of the control group, showing no significant difference (P>0.05). But the screw back-out distance was significantly shorter in the trial group than in the control group (P<0.05). The incidence of internal fixation failure in the trial group (4 cases) was significantly lower than that in the control group (14 cases) (P<0.05). The incidence of femoral neck shortening and the change of neck-shaft angle at 1 year after operation were significantly lower in the trial group than in the control group (P<0.05). The Harris score at last follow-up was significantly higher in the trial group than in the control group (P<0.05). Compared with the partial threaded cannulated screws, the full threaded cannulated compression screws can effectively maintain fracture reduction, avoid femoral neck shortening, and internal fixation failure. It is a better choice for femoral neck fracture.

Geometry and bone mineral density determinants of femoral neck strength changes following exercise

Physical exercise induces spatially heterogeneous adaptation in bone. However, it remains unclear where the changes in BMD and geometry have the greatest impact on femoral neck strength. The aim of this study was to determine the principal BMD-and-geometry changes induced by exercise that have the greatest effect on femoral neck strength. Pre- and post-exercise 3D-DXA images of the proximal femur were collected of male participants from the LIFTMOR-M exercise intervention trial. Meshes with element-by-element correspondence were generated by morphing a template mesh to each bone to calculate changes in BMD and geometry. Finite element (FE) models predicted femoral neck strength changes under single-leg stance and sideways fall load. Partial least squares regression (PLSR) models were developed with BMD-only, geometry-only, and BMD-and-geometry changes to determine the principal modes that explained the greatest variation in neck strength changes. The PLSR models explained over 90% of the strength variation with 3 PLS components using BMD-only (R2 > 0.92, RMSE < 0.06 N) and 8 PLS components with geometry-only (R2 > 0.93, RMSE < 0.06 N). Changes in the superior neck and distal cortex were most important during single-leg stance while the superior neck, medial head, and lateral trochanter were most important during a sideways fall. Local changes in femoral neck and head geometry could differentiate the exercise groups from the control group. Exercise interventions may target BMD changes in the superior neck, inferior neck, and greater trochanter for improved femoral neck strength in single-leg stance and sideways fall.

The effect of pharmacological cessation and restoration of menstrual cycle on bone metabolism in premenopausal women with endometriosis.

GnRH-analogs induce bone loss. We aimed to investigate the effects of goserelin-induced menstrual cessation (MC) and subsequent menstrual restoration (MR) on bone metabolism (BM). In this prospective cohort study, premenopausal women (PMW) with histologically verified endometriosis (n=21) received goserelin monthly for 6months (6m) resulting in MC and were followed up for another 6m after MR (12m). Age- and BMI-matched healthy PMW (n=20) served as controls for bone mineral density (BMD) measurements. The primary endpoint was changes in lumbar spine (LS)-BMD at 6m and 12m; Secondary endpoints were changes in femoral neck (FN)-BMD, bone turnover markers (P1NP and CΤx), sclerostin, and expression of bone-related circulating microRNAs (miRNAs) at 6m and 12m. Goserelin-induced MC reduced LS- and FN-BMD at 6m (both p<0.001). From 6m to 12m, LS-BMD increased (p<0.001) but remained below baseline values (p=0.012), whereas FN-BMD remained stable (p=1.000). CTx and P1NP levels increased at 6m (both p<0.001) and decreased at 12m (p<0.001 and p=0.013, respectively), while CTx (p=1.000) alone and not P1NP (p=0.020) returned to baseline. Sclerostin levels did not change. Relative expression of miRNAs targeting RUNX 2 and beta-catenin was significantly downregulated at 6m compared to baseline (p<0.001), while the expression of miRNAs targeting osteoblast and osteoclast function at both directions demonstrated a robust increase (up to 400fold) at 12m (p<0.001). Six months of goserelin-induced MC lead to significant bone loss associated with increased bone turnover and changes in the expression of bone-related miRNAs, changes that are only partially reversed at 6m after MR.

Pathways linking activity, adiposity, and inflammation to bone mineral density in women and men from NHANES 2007 to 2010.

Age, sedentary activity, central adiposity, and inflammation have all been independently associated with bone mineral density (BMD). We assessed how the effects of sedentary activity and central adiposity on BMD of the lumbar spine and femoral neck change across early to late adulthood and whether these relationships are mediated by inflammation. We analyzed data from 7135 women and men 20 years of age and older from NHANES 2007 to 2010. Anthropometrics, sedentary activity (min/day), serum CRP (mg/dl), and BMD (gm/cm2 measured by DXA scans) at the femoral neck and lumbar spine. Data were compared by age and sex groups and through causal mediation analysis. The effect of waist circumference on BMD was significantly mediated by serum CRP at both skeletal sites in men and at the femoral neck in women. Sedentary activity did not have a direct relationship to BMD but was mediated by waist circumference in men. Least square means differed significantly by sex and age groups with a general age-related decline in BMD at both skeletal sites. We found that central adiposity, independent of overall body size and composition as measured through BMI, has an inverse relationship with BMD that is mediated by serum CRP. In addition, the negative impact of increased sedentism acted through changes in central adiposity (waist circumference) but only in men. Although low bone density and osteoporosis are often considered degenerative diseases that primarily impact postmenopausal women, our findings show that sedentary activity and central adiposity impact bone density beginning in early adulthood in both women and men.

Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg).

ContextBariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with an increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health.ObjectiveTo compare changes in bone mineral density and markers of bone turnover 1 year after SG and RYGB.Design, Setting, Patients, and InterventionsRandomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcome was diabetes remission. Patients with severe obesity and type 2 diabetes were randomized and allocated (1:1) to SG or RYGB.Main Outcome MeasuresChanges in areal bone mineral density (aBMD) and bone turnover markers.ResultsFemoral neck, total hip, and lumbar spine aBMD, but not total body aBMD, decreased significantly more after RYGB (n = 44) than after SG (n = 48) (mean [95% confidence interval] between group differences -2.8% [-4.7 to -0.8], -3.0% [-5.0 to -0.9], -4.2% [-6.4 to -2.1], and -0.5% [-1.6 to 0.6], respectively). The increase in procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1) were approximately 100% higher after RYGB than after SG (between group difference at 1 year, both P < 0.001). The changes in femoral neck, total hip, and lumbar spine aBMDs and the changes in P1NP and CTX-1 were independently associated with the surgical procedure (all P < 0.05) and not weight change.ConclusionsRoux-en-Y gastric bypass was associated with a greater reduction in aBMD and a greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.

Efficacy and safety of sodium RISedronate for glucocorticoid-induced OsTeoporosis with rheumaTOid arthritis (RISOTTO study): A multicentre, double-blind, randomized, placebo-controlled trial

Objective No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. Methods This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. Results Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92–5.05] vs Placebo: 0.12% [95% CI: −2.07 to 2.30], p < .0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. Conclusion Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.

The three-year effect of a single zoledronate infusion on bone mineral density and bone turnover markers following denosumab discontinuation in women with postmenopausal osteoporosis.

In women with postmenopausal osteoporosis denosumab discontinuation is associated with rapid bone loss that could be potentially prevented by a single zoledronate infusion for two years. The longer-term effects, however, of zoledronate treatment are unknown. We aimed to study the effect of a single zoledronate infusion during the third year following denosumab discontinuation, in initially treatment-naive postmenopausal women who became osteopenic after 2.4±0.2years of denosumab therapy. We report the 1-year follow-up results of a single arm observational extension of a previously reported 2-year multicenter prospective randomized clinical trial. The primary endpoint of this extension was the change in lumbar spine bone mineral density (LS-BMD); secondary endpoints were changes in femoral neck (FN)-BMD and markers of bone turnover (BTM) during the 3rd year from the zoledronate infusion. Changes are presented as mean and SEM. LS-BMD did not change significantly at year 3 compared to year 2(-1.35±1.1%, p=1.00) and compared to baseline (-1.96±1.44%, p=1.00). FN-BMD values did not change while serum P1NP values decreased and CTX values remained unchanged during the third-year of the follow-up. In 4 of the 23 studied women BMD values returned to the osteoporotic range at 3years. A single i.v. infusion of zoledronate 5mg, given 6months after the last injection of denosumab therapy maintains for three years BMD gains in the majority of patients previously treated with denosumab for an approximate period of 2.5years. Follow-up of patients is, however, recommended because about one-fifth of treated women will require additional antiosteoporotic treatment.

Reduction in Aortic Pulse Wave Velocity Is Associated with a Short-Term Reduction in Dual-Energy X-Ray Absorptiometry Lumbar Spine Bone Mineral Density T Score

Introduction: Increased vascular stiffness is a risk factor for mortality. We wished to determine whether changes in vascular stiffness are associated with changes in bone mineral density (BMD) in peritoneal dialysis patients. Methods: We measured vascular stiffness by aortic pulse wave velocity (aPWV) and BMD by dual electron absorptiometry (DXA) scanning and compared T scores to compensate for differences in patient ages and gender. Results: Twenty-four patients had repeat aPWV measurements and DXA scans, median 12.4 months apart. aPWV decreased in 15 and increased in 9. As there were more women in the group with an increase in aPWV, we used gender-adjusted DXA T scores Total body T scores fell in both groups, but median T scores remained positive for those with an increase in aPWV, whereas negative T scores on both scans for those with a decrease in or stable aPWV. Lumbar spine T scores fell in those with a reduction in aPWV (–1.6 [–2.4 to 0.6] to –2.1 [–2.4 to 0.3], p < 0.05), whereas there was no significant decrease in those with an increase in aPWV (–0.5 [–1.1 to 0.15] to –0.7 [–1.7 to 0.6]). There were no changes in femoral neck T scores. Conclusions: Our study reinforces the hypothesis of a link between bone disease and vascular disease in dialysis patients. Lumbar spine DXA includes imaging of the aorta and will include aortic calcification, and as such a reduction in lumbar spine T score without a change in femoral neck T score suggests a reduction in aortic calcification. Although our study requires additional confirmation, our data would suggest that changes in aPWV could be used as a surrogate for changes in vascular calcification in the investigation of interventions designed to reduce vascular calcification.

Biological sex variation in bone mineral density in the cranium and femur

ObjectivesSex and age trends in bone mineral density (BMD) play an important role in the estimation of age-at-death (AAD) of unidentified human remains. Current methodologies lack the ability to precisely estimate age in older individuals. In this study, BMD of the cranium and femur measured by DXA were examined to establish their applicability for age estimation in older adults. BMD as measured by DXA, is most commonly used clinically for prediction of osteoporotic fracture risk. We hypothesized that weight-bearing and non-weight-bearing bones, the femur and cranium, respectively, would provide valuable insights for aging. MethodsThe sample consists of 32 sets of excised cranial fragments from the Regional Forensic Center, Johnson City, Tennessee and 41 associated crania and femora from the North Carolina Office of the Chief Medical Examiner. All crania and femora were scanned using a Hologic (R) DXA scanner and data were analyzed using Student t-tests, Loess regression, and ANOVA. ResultsStudent t-tests indicate a significant relationship between the sexes and cranial BMD and a significant relationship between age cohorts and femoral neck BMD. The Loess regression showed different aging patterns in the cranium for females and males older than 55. And the ANOVA showed changes in femoral neck after age 55. ConclusionsThese results indicate age and sex dependent changes in BMD especially for individuals over the age of 55, which offers improvement from current aging methods for older individuals. Further research using a larger sample size could improve the predictive capabilities of the model.

Long-term use of angiotensin-converting enzyme inhibitors protects against bone loss in African-American elderly men.

There is evidence of bone mass preservation in patients receiving ACEis, commonly used to treat hypertension. However, limitations of previous studies include being cross-sectional or only including a short-term follow-up of patients using ACEi and including patients with diabetes, which affects bone metabolism. None of the previous studies described effects of ACEi stratified by race. The objective of this study was to investigate differences in changes in bone mineral density (BMD) in older adults who suffer from hypertension and had reported ACEi use during each study visit for at least 9years during the study, stratified by gender and race. We used data from the Dynamics of Health, Aging and Body Composition (HABC) study, which enrolled 3075 community-dwelling older white and black individuals. We compared changes in femoral neck, total hip, and whole-body BMD after either no use of ACEi (n=580) or long-term use (at least 9years) of ACEi (n=239) in HABC participants with hypertension and no known diagnosis of diabetes mellitus. Overall, BMD values significantly decreased for all subgroups over time. In the stratified multivariate analysis, long-term use of ACEi was associated with a reduced rate of decline for all three BMD measures among black men, but no significant effect was observed in the other subgroups. Our findings show a gender- and race-specific effect of ACEi in the prevention of age-associated bone loss that warrants further evaluation.

Is Obesity a Cardiovascular Risk Factor? Correlation of DXA Derived Fat Components & Cardiometabolic Features

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. Trial registration: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Total Body Lean Mass, but Not Appendicular Lean Mass Least Significant Change Should be Calculated Separately for Older Men and Women

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. Trial registration: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Morgan line and its relationship with distraction index, angle of inclination and degenerative joint disease in the diagnosis of canine hip dysplasia

ABSTRACT We evaluated 160 hip joint radiographs of 40 dogs of different large breeds (25 females and 15 males) from the metropolitan area of Belo Horizonte, Minas Gerais, Brazil. The radiographs of each dog were obtained at two different stages: stage 1 (mean 7.23 months) and stage 2 (mean 14.25). The conventional radiographic method (CRM) and the radiographic distraction method (RDM) were used, carried out in both stages. CRM measured the Norberg angle (NA), the angle of inclination (AI) and evaluated the presence of degenerative joint disease (DJD). The MRD was performed to establish the distraction index (DI). The aims were to evaluate the presence of the Morgan line and other signs of DJD and correlate them with the degree of canine hip dysplasia (CHD) and also check if the DI greater than 0.3 (first stage) was associated with the presence of ML (second stage). It was found that DI, AI and changes of femoral neck and the formation of osteophytes were associated with the presence of ML. It was observed that if the DI is greater than 0.3 at the first stage, the chance of a positive outcome of ML in the second stage increases by 7.2 times. Thus, 49 joints showed DI &gt; 0.3 at the first stage, in which 31 (63.3 %) presented ML at the second stage. Of the 31 animals that showed DI ≤ 0.3 at first, six (19.4%) had LM at the second stage. There has been a significant association between the presence of ML and the degree of CHD. The more severe the CHD, the higher the percentage of positive ML results. Thus, among the 24 (60 %) animals that showed ML, 11 (45.83 %) were classified as severe dysplastics, 5 (20.83%) as moderate and 8 (33.33 %) as mild. None of the animals classified as normal or borderline presented ML. Among the 8 animals classified as mild dysplastics, 5 showed only ML as DJD.

Longitudinal associations between bone and adipose tissue biochemical markers with bone mineralization in boys during puberty.

BackgroundWe investigated longitudinal relationships between the biochemical markers of bone and adipose tissue with bone mineral content (BMC), bone mineral density (BMD), moderate-to-vigorous physical activity (MVPA) and sedentary time (SED) in pubertal boys.MethodsNinety-six boys (11.9 ± 0.6 years old) were measured at baseline, after 12 and 24 months. Body composition (fat mass [FM], lean body mass [LBM]), and whole body (WB), lumbar spine (LS) and femoral neck (FN) BMD and BMC were assessed. Additionally, serum leptin, adiponectin, osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) were measured.ResultsOC had a strong longitudinal inverse effect on changes in WB_BMD (p < 0.001) and LS_BMD (p = 0.021), while CTX had an inverse effect only on changes in FN_BMD (p = 0.011). Leptin had an inverse effect on changes in WB_BMC/WB_BMD (p = 0.001), FN_BMD (p = 0.002) and LS_BMD (p = 0.001). MVPA showed a longitudinal inverse effect on changes in leptin (p = 0.030), however no longitudinal effect of SED to biochemical markers of bone and adipose tissue was found.ConclusionsBone metabolism markers have negative effect on bone mineral accrual during puberty. Increases in MVPA affect leptin, suggesting a positive link of MVPA through leptin metabolism on increases in bone mineralization during puberty.

Evaluation of Quantitative Computed Tomography Cortical Hip Quadrant in a Clinical Trial With Rosiglitazone: A Potential New Study Endpoint

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. Trial registration: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Teriparatide Increases Bone Formation and Bone Mineral Density in Adult Women With Anorexia Nervosa

Anorexia nervosa (AN), a prevalent psychiatric disorder predominantly affecting women, is characterized by self-induced starvation and low body weight. Increased clinical fractures are common, and most women have low bone mineral density (BMD). Previously investigated treatments have led to no or modest increases in BMD in AN. Our objective was to investigate the effect of teriparatide (TPT; human PTH[1-34]), an anabolic agent, on low bone mass in women with AN. This randomized, placebo-controlled trial at a clinical research center included 21 women with AN: 10 (mean age ± SEM, 47 ± 2.7 years) treated with TPT and 11 (47.1 ± 2.3 years) treated with placebo. TPT (20 μg s.c.) or placebo was administered for 6 months. Our primary outcome measure was change in BMD of the spine and hip by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in serum N-terminal propeptide of type 1 procollagen (P1NP), C-terminal collagen cross-links, sclerostin, and IGF-1 levels. At 6 months, spine BMD increased significantly more with TPT (posteroanterior spine, 6.0% ± 1.4%; lateral spine, 10.5% ± 2.5%) compared with placebo (posteroanterior spine, 0.2% ± 0.7%, P < .01; lateral spine, -0.6% ± 1.0%; P < .01). The results remained significant after controlling for baseline body mass index, P1NP, and IGF-1. Changes in femoral neck (P = .4) and total hip (P = 0.8) BMD were comparable in both groups, as were changes in weight. Serum P1NP levels increased after 3 months of TPT treatment and remained at this higher level at 6 months, whereas P1NP levels were unchanged in the placebo group (P = .02). TPT was well-tolerated by all subjects. This study demonstrates that TPT administration increases spine BMD substantially after only 6 months of therapy in women with AN.

Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis—a double-blind, randomized, dose-finding study

The efficacy and safety of oral placebo or odanacatib 10, 25, or 50 mg once weekly for 52 weeks were evaluated in a double-blind, randomized, multi-center study in Japanese female and male patients with osteoporosis. Odanacatib is a selective and reversible cathepsin K inhibitor that decreases bone resorption and increases bone mineral density (BMD). The primary efficacy endpoint was percent change from baseline to week 52 in lumbar spine BMD. Secondary endpoints included percent change in total hip, femoral neck, and trochanter BMD and in bone biomarkers after treatment for 52 weeks. In this study, 286 patients [94% female, mean age (SD) 68.2 (7.1) years] were included in the analysis. The least-squares mean percent changes from baseline to week 52 in the groups receiving placebo, 10, 25 and 50 mg of odanacatib for lumbar spine (L1~L4) BMD were 0.5, 4.1, 5.7, and 5.9% and for total hip BMD were -0.4, 1.3, 1.8, and 2.7%, respectively. The changes in femoral neck and trochanter BMD were similar to those at the total hip. Bone turnover markers were reduced in a dose-dependent manner. However, the effects of odanacatib on bone formation markers were less compared with the effects on bone resorption markers. Tolerability and safety profiles were similar among all treatment groups with no dose-related trends in any adverse events. Weekly odanacatib treatment for 52 weeks increased BMD at the lumbar spine and at all hip sites in a dose-dependent manner and was well tolerated in Japanese patients with osteoporosis.

Effects of ground and joint reaction force exercise on lumbar spine and femoral neck bone mineral density in postmenopausal women: a meta-analysis of randomized controlled trials

BackgroundLow bone mineral density (BMD) and subsequent fractures are a major public health problem in postmenopausal women. The purpose of this study was to use the aggregate data meta-analytic approach to examine the effects of ground (for example, walking) and/or joint reaction (for example, strength training) exercise on femoral neck (FN) and lumbar spine (LS) BMD in postmenopausal women.MethodsThe a priori inclusion criteria were: (1) randomized controlled trials, (2) exercise intervention ≥ 24 weeks, (3) comparative control group, (4) postmenopausal women, (5) participants not regularly active, i.e., less than 150 minutes of moderate intensity (3.0 to 5.9 metabolic equivalents) weight bearing endurance activity per week, less than 75 minutes of vigorous intensity (> 6.0 metabolic equivalents) weight bearing endurance activity per week, resistance training < 2 times per week, (6) published and unpublished studies in any language since January 1, 1989, (7) BMD data available at the FN and/or LS. Studies were located by searching six electronic databases, cross-referencing, hand searching and expert review. Dual selection of studies and data abstraction were performed. Hedge’s standardized effect size (g) was calculated for each FN and LS BMD result and pooled using random-effects models. Z-score alpha values, 95%confidence intervals (CI) and number-needed-to-treat (NNT) were calculated for pooled results. Heterogeneity was examined using Q and I2. Mixed-effects ANOVA and simple meta-regression were used to examine changes in FN and LS BMD according to selected categorical and continuous variables. Statistical significance was set at an alpha value ≤0.05 and a trend at >0.05 to ≤ 0.10.ResultsSmall, statistically significant exercise minus control group improvements were found for both FN (28 g’s, 1632 participants, g = 0.288, 95% CI = 0.102, 0.474, p = 0.002, Q = 90.5, p < 0.0001, I2 = 70.1%, NNT = 6) and LS (28 g’s, 1504 participants, g = 0.179, 95% CI = −0.003, 0.361, p = 0.05, Q = 77.7, p < 0.0001, I2 = 65.3%, NNT = 6) BMD. Clinically, it was estimated that the overall changes in FN and LS would reduce the 20-year relative risk of osteoporotic fracture at any site by approximately 11% and 10%, respectively. None of the mixed-effects ANOVA analyses were statistically significant. Statistically significant, or a trend for statistically significant, associations were observed for changes in FN and LS BMD and 20 different predictors.ConclusionsThe overall findings suggest that exercise may result in clinically relevant benefits to FN and LS BMD in postmenopausal women. Several of the observed associations appear worthy of further investigation in well-designed randomized controlled trials.