Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis.

Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. PURPOSE: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. METHODS: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], - 3.3; total hip [TH], - 2.6; femoral neck [FN], - 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. RESULTS: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006-1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). CONCLUSIONS: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.

The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study.

STUDY DESIGN: Randomized double blind, placebo-controlled trial. OBJECTIVES: To examine the effect of early intravenous zoledronic acid (ZA) on bone markers and areal bone mineral density (aBMD) in persons with acute ASIA Impairment Scale (AIS) A traumatic spinal cord injury (SCI). SETTING: Two inpatient rehabilitation units. METHODS: Thirteen men, 2 women, aged 19-65, C4-T10 AIS A SCI, received 5 mg intravenous ZA vs. placebo 12-21 days post injury. Markers of bone formation (procollagen N-1 terminal propeptide [P1NP]), bone resorption (serum C-telopeptide [CTX]), and aBMD by dual-energy X-ray absorptiometry (DXA) for hip (femur-proximal, intertrochanteric, neck), and knee (distal femur, proximal tibia) were obtained at baseline, 2 weeks post infusion (P1NP, CTX only), 4 and 12 months post injury. RESULTS: P1NP remained unchanged, while CTX decreased in ZA but increased in controls at 2 weeks (mean difference = -97%, p < 0.01), 4 months (mean difference = -54%, p < 0.05), but not 12 months (mean difference = 3%, p = 0.23). Changes in aBMD at the hip favored ZA at 4 months (mean difference 10.3-14.1%, p < 0.01) and 12 months (mean difference 10.8-13.1%, p < 0.02). At 4 months, changes in aBMD favored ZA at the distal femur (mean difference 6.0%, 95% CI: 0.7-11.2, p < 0.03) but not proximal tibia (mean difference 8.3%, 95% CI: -6.9 to 23.6, p < 0.23). Both groups declined in aBMD at 12 months, with no between group differences. CONCLUSION: ZA administered ≤21 days of complete traumatic SCI maintains aBMD at the hip and distal femur at 4 months post injury. This effect is partially maintained at 12 months.

Regional improvements in lumbosacropelvic Hounsfield units following teriparatide treatment.

OBJECTIVE: Opportunistic Hounsfield unit (HU) determination from CT imaging has been increasingly used to estimate bone mineral density (BMD) in conjunction with assessments from dual energy x-ray absorptiometry (DXA). The authors sought to compare the effect of teriparatide on HUs across different regions in the pelvis, sacrum, and lumbar spine, as a surrogate measure for the effects of teriparatide on lumbosacropelvic instrumentation. METHODS: A single-institution retrospective review of patients who had been treated with at least 6 months of teriparatide was performed. All patients had at least baseline DXA as well as pre- and post-teriparatide CT imaging. HUs were measured in the pedicle, lamina, and vertebral body of the lumbar spine, in the sciatic notch, and at the S1 and S2 levels at three different points (ilium, sacral body, and sacral ala). RESULTS: Forty patients with an average age of 67 years underwent a mean of 20 months of teriparatide therapy. Mean HUs of the lumbar lamina, pedicles, and vertebral body were significantly different from each other before teriparatide treatment: 343 ± 114, 219 ± 89.2, and 111 ± 48.1, respectively (p < 0.001). Mean HUs at the S1 level for the ilium, sacral ala, and sacral body were also significantly different from each other: 124 ± 90.1, -10.7 ± 61.9, and 99.1 ± 72.1, respectively (p < 0.001). The mean HUs at the S2 level for the ilium and sacral body were not significantly different from each other, although the mean HU at the sacral ala (-11.9 ± 52.6) was significantly lower than those at the ilium and sacral body (p = 0.003 and 0.006, respectively). HU improvement occurred in most regions following teriparatide treatment. In the lumbar spine, the mean lamina HU increased from 343 to 400 (p < 0.001), the mean pedicle HU increased from 219 to 242 (p = 0.04), and the mean vertebral body HU increased from 111 to 134 (p < 0.001). There were also significant increases in the S1 sacral body (99.1 to 130, p < 0.05), S1 ilium (124 vs 165, p = 0.01), S1 sacral ala (-10.7 vs 3.68, p = 0.04), and S2 sacral body (168 vs 189, p < 0.05). CONCLUSIONS: There was significant regional variation in lumbar and sacropelvic HUs, with most regions significantly increasing following teriparatide treatment. The sacropelvic area had lower HU values than the lumbar spine, more regional variation, and a higher degree of correlation with BMD as measured on DXA. While teriparatide treatment resulted in HUs > 110 in the majority of the lumbosacral spine, the HUs in the sacral ala remained suggestive of severe osteoporosis, which may limit the effectiveness of fixation in this region.

Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Teriparatide treatment exerts differential effects on the central and peripheral skeleton: results from the MOAT study.

The central and peripheral skeleton was characterised using imaging techniques during 104 weeks of teriparatide treatment. Teriparatide exerts differential effects on the central and the peripheral skeleton. Overall, we did not observe a change in total body bone mineral. Our conclusions are constrained by the study limitations. INTRODUCTION: Teriparatide stimulates bone formation and resorption and therefore can cause bone gain and loss. We simultaneously characterised the central and peripheral skeleton using imaging techniques to better understand the mechanism of action of teriparatide. METHODS: Postmenopausal, osteoporotic women (n = 20, 65.4 ± 5.5 years) were recruited into a 104-week study of teriparatide. Imaging techniques included DXA, quantitative computed tomography (QCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Total lumbar spine areal bone mineral content (aBMC) (+ 11.2%), total lumbar spine areal bone mineral density (aBMD) (+ 8.1%), subregional thoracic spine aBMD (+ 7.5%), lumbar spine aBMC (+ 23.5%), lumbar spine aBMD (+ 11.9%), pelvis aBMC (+ 9.3%), and pelvis aBMD (+ 4.3%) increased. However, skull aBMC (- 5.0%), arms aBMC (- 5.1%), legs aBMC (- 2.9%), and legs aBMD (- 2.5%) decreased. Overall, we did not observe a change in total body bone mineral. Increases in L1-L3 volumetric BMD (vBMD) (+ 28.5%) occurred but there was no change in total proximal femur vBMD. Radius and tibia cortical vBMD (- 3.3 and - 3.4%) and tissue mineral density (- 3.2 and - 3.8%) decreased and there was an increase in porosity (+ 21.2 and + 10.3%). Tibia, but not radius, trabecular inhomogeneity (+ 3.2%), and failure load (+ 0.2%) increased, but cortical thickness (- 3.1%), area (- 2.9%), and pore volume (- 1.6%) decreased. CONCLUSIONS: Teriparatide exerts differential effects on the central and the peripheral skeleton. Central trabecular vBMD (L1-L3) is improved, but there is a concomitant decrease in peripheral cortical vBMD and an increase in porosity. Overall, we did not observe a change in total body bone mineral. We acknowledge that our conclusions may be speculative and are constrained by the technical limitations of the imaging techniques used, the lack of a control group, and the small sample size studied.

Efficacy of discontinuing risedronate for patients with systemic lupus erythematosus: a prospective study.

Objective The objective of this study is to investigate the effectiveness of discontinuation of risedronate for patients with systemic lupus erythematosus (SLE) treated with glucocorticoid (GC). Methods The participants were patients with SLE treated with prednisolone (PSL) ≥ 2 mg/day and risedronate for at least three years. Lumbar spine and total hip bone mineral density (BMD) measurements were taken at baseline and 24 and 48 weeks after discontinuation of risedronate, and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks. Results A total of 36 patients were enrolled, 25 of whom discontinued risedronate. The mean age was 46.8 ± 11.2 years, and 23 were female. The mean duration of GC treatment was 14.8 ± 11.4 years, the mean dose of PSL was 7.8 ± 3.9 mg/day, and the mean duration of risedronate was 5.8 ± 2.4 years. Seventeen patients showed decreased lumbar spine BMD at 48 weeks after discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42% ± 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48 weeks after discontinuation of risedronate, with a mean total hip BMD decrease of 0.99% ± 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) ≥ 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48 weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One patient developed a clinical fracture of the lumbar spine at 20 weeks. Conclusions Discontinuation of risedronate treatment in patients with SLE who had received GC therapy led to decreases in lumbar spine and total hip BMD, particularly in patients with high baseline serum TRACP-5b levels.

High incidence of aseptic hip necrosis in Hodgkin lymphoma patients treated with escalated BEACOPP receiving methylprednisolone.

BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. AIMS: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. METHODS: We identified 26 patients treated with eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.

Variability of Denosumab densitometric response in postmenopausal osteoporosis.

The objective of our prospective study is to specify the variability of densitometric response to Denosumab, given in the second line, and to try to understand the reasons. All menopausal patients with primary osteoporosis, treated by Denosumab in our centre from 2014 to 2015, were included in this open prospective work. At T0, the patient's age, type of fracture, and previous treatments were collated. At T0 and T1, after 1 year of treatment by Dmab, a DXA of the spine and the hip and a determination of CTX were performed. Sixty-three patients aged 68.8 ± 8.3 years were included. The median number of treatments prescribed for osteoporosis before switch to Denosumab was 2.4. The median duration of these treatments was 7.2 years. At T1, CTX was less than 33 pg/ml (minimum threshold for our assay kit) in all patients. The median BMD in the spine increased by + 5.44% compared to T0. 14 patients in the upper quartile had a median BMD gain in the spine of + 11.07%. Fourteen patients in the lower quartile had a median BMD gain in the spine of + 0.6%. Only the duration of previous treatments, which was greater in the non-responder group, differed between these two groups. In the total cohort, the spinal densitometric gain was negatively correlated with the age of the patient at baseline (p = 0.04), the duration of previous treatment (p = 0.02), and positively with the CTX level (p = 0.05). The Dmab densitometric response is highly variable, partly explained by the duration of previous treatments and the level of bone resorption at initiation of treatment.

Incorporating 18FDG-PET-defined pelvic active bone marrow in the automatic treatment planning process of anal cancer patients undergoing chemo-radiation.

BACKGROUND: To investigate whether the incorporation of 18FDG-PET into the automatic treatment planning process may be able to decrease the dose to active bone marrow (BM) for locally advanced anal cancer patients undergoing concurrent chemo-radiation (CHT-RT). METHODS: Ten patients with locally advanced anal cancer were selected. Bone marrow within the pelvis was outlined as the whole outer contour of pelvic bones or employing 18FDG-PET to identify active BM within osseous structures. Four treatment planning solutions were employed with different automatic optimization approaches toward bone marrow. Plan A used iliac crests for optimization as per RTOG 05-29 trial; plan B accounted for all pelvic BM as outlined by the outer surface of external osseous structures; plan C took into account both active and inactive BM as defined using 18FDG-PET; plan D accounted only for the active BM subregions outlined with 18FDG-PET. Dose received by active bone marrow within the pelvic (ACTPBM) and in different subregions such as lumbar-sacral (ACTLSBM), iliac (ACTIBM) and lower pelvis (ACTLPBM) bone marrow was analyzed. RESULTS: A significant difference was found for ACTPBM in terms of Dmean (p = 0.014) V20 (p = 0.015), V25 (p = 0.030), V30 (p = 0.020), V35 (p = 0.010) between Plan A and other plans. With respect to specific subsites, a significant difference was found for ACTLSBM in terms of V30 (p = 0.020)), V35 (p = 0.010), V40 (p = 0.050) between Plan A and other solutions. No significant difference was found with respect to the investigated parameters between Plan B,C and D. No significant dosimetric differences were found for ACTLSPBM and ACTIBM and inactive BM subregions within the pelvis between any plan solution. CONCLUSIONS: Accounting for pelvic BM as a whole compared to iliac crests is able to decrease the dose to active bone marrow during the planning process of anal cancer patients treated with intensity-modulated radiotherapy. The same degree of reduction may be achieved optimizing on bone marrow either defined using the outer bone contour or through 18FDG-PET imaging. The subset of patients with a benefit in terms of dose reduction to active BM through the inclusion of 18FDG-PET in the planning process needs further investigation.

Assessment of semaphorin 3A and its role in bone remodelling in a group of ankylosing spondylitis patients.

OBJECTIVES: Several molecules are involved in the pathogenesis of new bone formation in ankylosing spondylitis (AS). The aim of the present study was to evaluate serum levels of semaphoring 3A in AS and to investigate any correlations with radiographic damage, disease activity, function and treatment. METHODS: AS patients who fulfilled the modified New York criteria were enrolled for this study. Healthy subjects were also enrolled as control group. BASDAI, ASDAS-CRP, BASMI, BASFI, patients and physician VAS, C-reactive protein and erythrocyte sedimentation rate were evaluated at baseline visit. Radiographs of the spine and pelvis performed within six months from the enrolment in the study were collected in all patients. Spinal damage was assessed using the mSASSS. Serum concentrations of semaphorin3A were assessed at baseline and after four months of therapy in patients who started an anti-TNF. RESULTS: Twenty healthy subjects and forty AS patients were enrolled in the study. Of these patients, 15 started anti-TNF therapy the day of baseline visit. Semaphorin3A serum concentrations [median (25th-75th)] were similar in AS patients [0.26 (0.20-0.31) ng/ml] and controls [0.28 (0.26-0.3) ng/ml; p=ns). No significant correlation was found between semaphorin 3A serum levels and radiographic damage index. Semaphorin 3A serum levels positively correlated with ESR values (rho=0.37, p=0.049) and with disease activity assessed by the physician VAS (rho=0.47, p<0.01). No differences were found in the semaphorin3A serum levels after 4 months, compared to baseline values. CONCLUSIONS: The results of the present study could contribute to the intriguing topic of bone remodelling in AS.

The Impact of Antihypertensive Medications on Bone Mineral Density and Fracture Risk.

PURPOSE OF REVIEW: This review summarizes the impact of thiazide diuretics on fracture risk in older hypertensive individuals. RECENT FINDINGS: We performed a post hoc evaluation of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a randomized, prospective, double blind hypertension study comparing a thiazide-like diuretic, a calcium channel blocker (CCB), and an angiotensin converting enzyme inhibitor (ACEi). We examined the risk of hip and pelvic fractures during the in-trial period (n = 22,180 participants; mean 4.9-year follow-up) and during the post-trial period using national data bases (n = 16,622 participants) (mean total follow-up 7.8 years). During the trial, participants randomized to the thiazide diuretic versus the CCB or the ACEi had a lower risk of fracture on adjusted analyses (HR 0.79 [95% CI, 0.63, 0.98], p = 0.04). Risk of fracture was significantly lower in participants randomized to the diuretic as compared to those randomized to the ACEi (HR 0.75 [95% CI, 0.58, 0.98]; p = 0.04), but not significantly different compared to the CCB (HR 0.87 [95% CI, 0.71, 1.09]; p = 0.17). Over the entire trial and post-trial period of follow-up, the cumulative incidence of fractures was non-significantly lower in participants assigned to the diuretic vs assignment to the ACEi or the CCB (HR 0.87 [0.74-1.03], p = 0.10) and versus each medication separately. These findings establish a benefit for thiazide diuretic treatment for the prevention of fractures versus other commonly used antihypertensive medications using prospective, randomized data. The effects of the thiazide diuretic on bone appear to be long lasting.

OPG, RANKL, and RANK gene polymorphisms and the bone mineral density response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia.

OBJECTIVE: The aim of the study was to explore the association between OPG, RANKL, and RANK gene variations and the bone mineral density (BMD) response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia. MATERIALS AND METHODS: In the present study, 40 single-nucleotide polymorphisms (SNPs) in the OPG, RANKL, and RANK genes were genotyped in 501 postmenopausal Chinese women with osteoporosis or osteopenia who were given alendronate (70 mg weekly) orally for 1 year. The BMD at the lumbar spine 1-4 (L1-L4), femoral neck, and total hip was measured. RESULTS: A total of 442 patients completed 1 year of alendronate therapy. The rs7239261 SNP of the RANK gene was significantly associated with baseline L1-L4 BMD (P=0.0004) after correction for age and BMI. Participants with the SNP A allele (C/A and A/A) had a higher BMD than those with the C/C genotype (C/A vs. C/C, P=0.001; A/A vs. C/C, P=0.025). Haplotypes AG of rs7239261-rs12969154, GG of rs3826619-rs11877530, and CACG of rs1805034-rs8083511-rs17069895-rs7231887 in the RANK gene were genetic protective factors toward a higher baseline L1-L4 BMD. No association was observed between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy. CONCLUSION: The RANK gene might contribute to genetic variability in L1-L4 BMD in postmenopausal Chinese women with osteoporosis or osteopenia. No evidence of an association between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy was found in postmenopausal Chinese women with osteoporosis or osteopenia.

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.

Cortical bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Prior studies reveal that bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) is mostly in the osteopaenic range and is associated with lifetime glucocorticoid dose. The forearm, a measure of cortical bone density, has not been evaluated. OBJECTIVE: We aimed to evaluate BMD at various sites, including the forearm, and the factors associated with low BMD in CAH patients. METHODS: Eighty CAH adults (47 classic, 33 nonclassic) underwent dual-energy-x-ray absorptiometry and laboratory and clinical evaluation. BMD Z-scores at the AP spine, total hip, femoral neck, forearm and whole body were examined in relation to phenotype, body mass index, current glucocorticoid dose, average 5-year glucocorticoid dose, vitamin D, 17-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulphate (DHEAS). RESULTS: Reduced BMD (T-score <-1 at hip, spine, or forearm) was present in 52% and was more common in classic than nonclassic patients (P = 0·005), with the greatest difference observed at the forearm (P = 0·01). Patients with classic compared to nonclassic CAH, had higher 17-hydroxyprogesterone (P = 0·005), lower DHEAS (P = 0·0002) and higher non-traumatic fracture rate (P = 0·0005). In a multivariate analysis after adjusting for age, gender, height standard deviation, phenotype and cumulative glucocorticoid exposure, higher DHEAS was independently associated with higher BMD at the spine, radius and whole body. CONCLUSION: Classic CAH patients have lower BMD than nonclassic patients, with the most affected area being the forearm. This first study of forearm BMD in CAH patients suggests that low DHEAS may be associated with weak cortical bone independent of glucocorticoid exposure.

Medical specialty-related adherence to anti-osteoporotic regimens in fragility hip fracture patients.

There is poor adherence in the management of osteoporotic fractures. We designed a study to investigate adherence to osteoporotic regimens among osteoporotic hip fracture patients and to analyze the risk factors associated with poor compliance. This retrospective chart-review study was carried out using a database of osteoporotic hip fracture patients at a medical center in Taiwan for the period 2001-2007. Adherence was assessed using compliance and persistence. Compliance was calculated by the medication possession ratio (MPR) and persistence by the time from treatment initiation to discontinuation. The MPR and corresponding risk factors for poor compliance (MPR < 80 %) were evaluated for year 1. The year 2 results were analyzed only for those subjects with good compliance (MPR ≥ 80 %) at the end of year 1. There were 366 osteoporotic hip fracture patients (323 women, 43 men) with a mean age of 73.9 ± 7.6 years. Of these, 53.8 % had good compliance for year 1 and 68.5 % for year 2. During 2 years of follow-up, the overall persistence ratio was 33.1 %. The risk factor associated with poor compliance in the first year was index prescription by orthopedists [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.10-2.59]. Subjects with hypertension (OR 0.69, 95 % CI 0.46-0.99) had good compliance. Index prescription by orthopedists (OR 2.44, 95 % CI 1.31-4.51) was the sole risk factor for poor compliance in year 2. In conclusion, although adherence to osteoporotic regimens was sub-optimal in hip fracture patients, the majority of patients' decreased adherence occurred within the first year. Medical specialties showed different adherences in both year 1 and year 2.

Efficacy and safety of odanacatib treatment for patients with osteoporosis: a meta-analysis.

The aim of this study was to evaluate the efficacy and safety of odanacatib (ODN) for the treatment of osteoporosis, using data in studies reported in the literature. We performed a literature search to compare the outcomes of applications of once-weekly ODN 50 mg and control. The outcomes of osteoporosis evaluated include primary outcome as bone mineral density (BMD) at different skeletal sites, and secondary outcomes, including adverse events (AEs), such as incidence of skin AEs, fracture, and serious adverse events (SAEs). Four trials were included. Mean difference (95% CI) of lumbar spine BMD was 3.41 (1.57-5.24) at 12 months and 4.89 (2.72-7.05) at 24 months; mean difference (95% CI) of femoral neck BMD was 1.90 (0.73-3.08) at 12 months and 3.85 (2.55-5.15) at 24 months; mean difference (95% CI) of total hip BMD was 2.65 (1.20-4.09) at 12 months and 3.70 (1.76-5.64) at 24 months; risk ratio (95% CI) of AEs was 0.98 (0.91-1.07); risk ratio (95% CI) of SAEs was 1.11 (0.72-1.72); risk ratio (95% CI) of skin AEs was 0.92 (0.63-1.35); and risk ratio (95% CI) of fracture was 0.34 (0.16-0.70). In this study, application of 50 mg ODN produced significantly greater BMD increases and lower fracture incidence than that of the control. In addition, ODN was generally well tolerated.

High-Dose Corticosteroid Use and Risk of Hip Osteonecrosis: Meta-Analysis and Systematic Literature Review.

The effect of varying corticosteroid regimens on hip osteonecrosis incidence remains unclear. We performed a meta-analysis and systematic literature review to determine osteonecrosis occurrences in patients taking corticosteroids at varying mean and cumulative doses and treatment durations, and whether medical diagnoses affected osteonecrosis incidence. Fifty-seven studies (23,561 patients) were reviewed. Regression analysis determined significance between corticosteroid usage and osteonecrosis incidence. Osteonecrosis incidence was 6.7% with corticosteroid treatment of >2 g (prednisone-equivalent). Systemic lupus erythematosus patients had positive correlations between dose and osteonecrosis incidence. Each 10 mg/d increase was associated with a 3.6% increase in osteonecrosis rate, and >20 mg/d resulted in a higher osteonecrosis incidence. Clinicians must be wary of osteonecrosis in patients on high corticosteroid regimens, particularly in systematic lupus erythematosus.

Insufficiency fractures in patients treated with pelvic radiotherapy and chemotherapy for uterine and cervical cancer.

Insufficiency fractures are recognised consequences of radiotherapy in gynaecological malignancy with reported incidences between 2.7% and 89%. We aimed to determine the incidence and risk factors for insufficiency fractures in patients receiving radical pelvic radiotherapy for uterine and cervical cancer. A case-note review was undertaken of patients treated between January 2007 and December 2008. Insufficiency fractures were identified from radiographs, computed tomography and magnetic resonance images. Chi-squared and Mann-Whitney tests were performed to determine associations between insufficiency fractures and chemotherapy, steroids and age. A total of 285 patients received pelvic radiotherapy, 137 with uterine and 148 with cervical cancer. Mean age was 59 years. A total of 144 patients received chemotherapy, 101 concurrently and 35 adjuvantly. Bone abnormalities affected 67 patients, 33 had pelvic insufficiency fractures, 12 had multiple fractures and 3 patients developed femoral head avascular necrosis. Use of chemotherapy was not associated with development of fractures (P = 0.949). However, cervical cancer patients had a significantly higher incidence of insufficiency fractures (P = 0.018) and bone pain (P = 0.03) compared with uterine cancer patients. This suggests concurrent chemotherapy may be a significant factor in increasing insufficiency fractures and bone morbidity in these patients and highlights a need for further research to identify, prevent and reduce these long-term complications.

[Pathophysiological grounds of reamberin application in complex treatment of disintegrated factures of pelvic bones].

The investigation showed that reamberin application in the complex treatment of patients with severe disintegrated fractures of pelvic bones is pathogenetically grounded. Despite polyetiological origin of critical conditions in the organism in this case, all these have a common pathophysiological basis of three main processes: hypoxia, intoxication, and immunosuppression. Succinic acid, which is contained in reamberin, is a substrate antihypoxant that stimulates the synthesis of restorative equivalents in the cell. A modifying effect of succinic acid on the processes of tissue metabolism, including cell respiration, LPO/AOS system, and synthesis of proteins, is the basis of pathophysiological ground of reamberin application in a complex treatment of patients with disintegrated fractures of pelvic bones.

The effect of angiotensin-converting enzyme inhibitor use on bone loss in elderly Chinese.

In this study we analyzed the independent effect of angiotensin-converting enzyme (ACE) inhibitor use on bone loss in elderly Chinese. The subjects were from two cohort studies which investigated the risk factors of osteoporotic fractures in Hong Kong-dwelling elderly Chinese. A total of 2161 subjects (1280 male, 881 female) were selected for this analysis. The results showed that unadjusted annualized percentage bone loss of male ACE inhibitor users was not different from non-users; however, female ACE inhibitor users had significantly greater bone loss both in total hip and femoral neck than non-users. After adjusting for significant confounders, female continuous ACE inhibitor users had significantly greater bone loss at total hip and femoral neck. In conclusion, continuous use of ACE inhibitors over 4 years was associated with increased bone loss in total hip and femoral neck in older Chinese women.