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Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures., Purpose: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated., Methods: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up., Results: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94])., Conclusion: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Introduction: We investigated the relationship between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and fracture in elderly women diagnosed with type 2 diabetes mellitus (T2DM) and newly prescribed antidiabetic medications (ADMs)., Material and Methods: We used the population-based cohort study data from the National Health Insurance Service of Korea (2013-2020). Women ≥65 years old with T2DM, who were newly prescribed ADMs other than glucagon-like peptide-1 receptor agonists and thiazolidinedione, and who had comprehensive health check-up data were included., Results: A total of 1,333 SGLT2i users were matched in a 1:2 ratio with 2,626 non-SGLT2i users. After propensity score matching, mean age, body mass index, number of ADMs, and other covariates were well-balanced between SGLT2i users and non-SGLT2i users. During the follow-up period, a higher incidence of vertebral fractures in SGLT2i users than in non-SGLT2i users (incidence rate 19.2 vs. 13.8 per 1,000 person-years; hazard ratio 1.40, 95 % confidence interval 1.00-1.96, p = 0.049). No significant difference was noted in other types of fracture., Conclusion: SGLT2i use showed an increased risk of vertebral fracture than non-SGLT2i use in elderly women. Although further validation is required, SGLT2i should be cautiously prescribed in older women due to the potential association with fracture risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide analogue of the human parathyroid hormone-related protein that has recently been approved for the treatment of postmenopausal osteoporosis. Its efficacy and safety have not been systematically evaluated. Therefore, studies on the efficacy and safety of abaloparatide could be of assistance in the clinical medication of postmenopausal osteoporosis. The aim of this study was to evaluate the clinical efficacy and safety of abaloparatide in postmenopausal osteoporosis., Methods: PubMed, Cochrane Library, EMBASE, and Web of Science databases were electronically searched from inception to July 6, 2023, for relevant randomized controlled trials. Two review authors independently conducted the study screening, quality assessment (based on the Risk of Bias Assessment Tool recommended in the Cochrane handbook), and data extraction. Outcome measures included bone mineral density (BMD), bone turnover and metabolic markers, incidence of fractures, and adverse events. Data analyses were processed by using Stata SE15., Findings: Ultimately, 8 randomized controlled trials, involving a total of 3705 postmenopausal women, were included. Meta-analysis showed that abaloparatide administration significantly increased the BMD of the lumbar vertebrae (standardized mean difference [SMD], 1.28 [95% CI, 0.81-1.76); I 2 = 78.5%]), femoral neck (SMD, 0.70 [95% CI, 0.17-1.23; I 2 = 75.7%]), and hip bone (SMD, 0.86 [95% CI, 0.53-1.20; I 2 = 60.4%]) in postmenopausal women compared with the control group. Type I procollagen N-terminal propeptide, a bone formation marker, was also elevated after abaloparatide administration. The incidence of vertebral fracture was lower in the abaloparatide group than in the control group (risk ratio, 0.13; 95% CI, 0.06-0.26; I 2 = 0%). There was no significant difference in the incidence of adverse events between the abaloparatide and the placebo groups (risk ratio, 1.03; 95% CI, 0.99-1.06; I 2 = 0%)., Implications: Abaloparatide has a protective effect on women with postmenopausal osteoporosis. It could reduce their risk for vertebral fracture; increase their BMD of the lumbar spine, femoral neck, and hip; and alleviate symptoms and complications of postmenopausal osteoporosis with considerable safety. Limitations of this study include not searching the gray literature and not performing a subgroup analysis. PROSPERO Registration No.: CRD42022370944., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome., Methods: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4)., Results: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001)., Conclusion: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Androgen deprivation therapy (ADT) for prostate cancer causes cancer treatment-induced bone loss (CTIBL), increases the fracture risk 2-3 times, and worsens life prognoses. The Japan Society of Bone and Mineral Research (JSBMR) created a CTIBL treatment manual in 2020; however, no study has validated its use in patients with ADT/CTIBL prostate cancer., Materials and Methods: This study classified 124 patients with prostate cancer without bone metastasis who received ADT into high- and low-risk groups using the JSBMR CTIBL algorithm. Comparisons were made with the period to incident vertebral fracture and the existing International Osteoporosis Foundation (IOF) classification., Results: The median age was 74 years; the median observation period was 81 months. At 1, 3, 5, 7, and 9 years, the prevalence of incident vertebral fractures was, respectively, 3.3%, 10.7%, 17.9%, 21.4%, and 31.2% in the entire population; 13%, 27%, 36%, 42%, and 58% in the high-risk group (19%); and 1%, 7%, 14%, 17%, and 25% in the low-risk group (81%). The hazard ratio between the two groups was 3.57 (p = 0.0004). Based on multivariate analysis, age, previous vertebral fracture and femoral neck bone density were significant risk factors for incidental vertebral fracture. The JSBMR had a hazard ratio of 3.26 (p = 0.04) relative to 1.13 (p = 0.84) for the IOF, indicating the JSBMR classification performed better., Conclusion: Taking preventive measures against fractures is necessary, including starting bone-modifying agents early in patients with a high fracture risk. The JSBMR CTIBL manual may be useful for this purpose., (© 2023. The Japanese Society Bone and Mineral Research.)

Among those who use of liver-enzyme inducing anticonvulsant medication for more than 2 years, 27% have a prevalent vertebral fracture on vertebral fracture assessment (VFA) lateral spine imaging. VFA imaging at the time of bone densitometry may be appropriate for older individuals who are chronic users of these medications., Purpose: It is unclear whether prevalent vertebral fractures are associated with use of anticonvulsant drugs, especially those that induce liver enzymes (LEI) that metabolize drugs and vitamin D. Our purpose was to estimate the prevalence of vertebral fracture on densitometric lateral spine images according to duration of prior anticonvulsant medication use., Methods: Our study population was 11,822 individuals (mean [sd] age 76.1 [6.8] years, 94% female) who had bone densitometry with VFA between 2010 and 2018. Cumulative prior exposure to LEI anticonvulsants (carbamazepine, phenobarbital, phenytoin, valproic acid, n = 538), non-LEI anticonvulsants (clonazepam, gabapentin, levetiracetam, others, n = 2786), and other non-clonazepam benzodiazepines (n = 5082) was determined using linked pharmacy records. Prevalent vertebral fractures were identified on VFA images using the modified ABQ method. Logistic regression models were used to estimate the association of anticonvulsant drug exposure with prevalent vertebral fractures., Results: Prevalence of one or more vertebral fractures was 16.1% for the entire analytic cohort, and 27.0%, 19.0%, and 18.5% for those with ≥ 2 years of prior LEI anticonvulsant use, non-LEI anticonvulsant use, and other benzodiazepine use, respectively. Adjusted for multiple covariates, use of prior LEI anticonvulsant medication for ≥ 2 years was associated with prevalent fracture on VFA (OR 1.48 [95% CI 1.04, 2.10])., Conclusion: LEI anticonvulsant use for ≥ 2 years is associated with higher vertebral fracture prevalence. Lateral spine VFA imaging at the time of bone densitometry may be appropriate for older individuals who have used LEI anticonvulsant medications for ≥ 2 years., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: Second fractures at the cemented vertebrae (SFCV) are often seen after percutaneous kyphoplasty, especially at the thoracolumbar junction. Our study aimed to develop and validate a preoperative clinical prediction model for predicting SFCV., Methods: A cohort of 224 patients with single-level thoracolumbar osteoporotic vertebral fractures (T11-L2) from 3 medical centers was analyzed between January 2017 and June 2020 to derive a preoperative clinical prediction model for SFCV. Backward-stepwise selection was used to select preoperative predictors. We assigned a score to each selected variable and developed the SFCV scoring system. Internal validation and calibration were conducted for the SFCV score., Results: Among the 224 patients included, 58 had postoperative SFCV (25.9%). The following preoperative measures on multivariable analysis were summarized in the 5-point SFCV score: bone mineral density (≤-3.05), serum 25-hydroxy vitamin D3 (≤17.55 ng/mL), standardized signal intensity of fractured vertebra on T1-weighted images (≤59.52%), C7-S1 sagittal vertical axis (≥3.25 cm), and intravertebral cleft. Internal validation showed a corrected area under the curve of 0.794. A cutoff of ≤1 point was chosen to classify a low risk of SFCV, for which only 6 of 100 patients (6%) had SFCV. A cutoff of ≥4 points was chosen to classify a high risk of SFCV, for which 28 of 41 (68.3%) had SFCV., Conclusion: The SFCV score was found to be a simple preoperative method for identification of patients at low and high risk of postoperative SFCV. This model could be applied to individual patients and aid in the decision-making before percutaneous kyphoplasty., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoporosis is a common consequence of long-term oral glucocorticoid therapy and the resulting fractures cause significant morbidity. Bone loss occurs rapidly after initiation of glucocorticoid therapy; the accompanying increase in risk of fracture is dose-dependent and occurs within a few months of starting therapy. The adverse effects of glucocorticoids on bone are mediated by inhibition of bone formation accompanied by an early but transient increase in bone resorption, due both to direct and indirect effects on bone remodelling. Fracture risk assessment should be performed as soon as possible after long-term glucocorticoid therapy (≥3 months) is initiated. FRAX can be adjusted for the dose of prednisolone but does not currently take fracture site, recency, or number into account and therefore may underestimate fracture risk, particularly in individuals with morphometric vertebral fractures. Vertebral fracture assessment should therefore be regarded as a routine part of fracture risk estimation in individuals receiving long-term glucocorticoid therapy. Bone protective therapy should be started promptly in individuals at high-risk, together with calcium and vitamin D supplements. Bisphosphonates are generally regarded as first-line options on the grounds of their low cost, but anabolic therapy should be considered as an alternative first-line option in very high-risk individuals., Competing Interests: Conflicts of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology.)

In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture., Purpose: To determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed., Methods: Japanese women aged at least 75 years were eligible for the study, if they had primary osteoporosis and if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks, followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period., Results: Between October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P < 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug., Conclusion: Once-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019., (© 2022. The Author(s).)

Introduction: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ)., Materials and Methods: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs., Results: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively., Conclusions: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly., (© 2022. The Japanese Society Bone and Mineral Research.)

Purpose: Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to examine whether physicians prescribe AOMs as soon as GC therapy is initiated, and whether a delay in AOM initiation affects hip and vertebral fracture incidence, using the nationwide health insurance claims database of Japan (NDBJ)., Methods: Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed for AOM use and hip and vertebral fracture events for the subsequent 1080 days in 2012-2018 were selected from NDBJ. Delay in AOM initiation was defined as the number of days without AOMs following GC therapy initiation. Associations between delay in AOM initiation and hip and vertebral fracture risk were evaluated by Cox proportional hazards regression., Results: In total, 92,143 women and 94,772 men were included in the analysis, of which only 39.3% of women and 28.5% of men received AOMs within 90 days from GC therapy initiation. Approximately, 15% of hip fractures and 30% of vertebral fractures occurred before AOM initiation in patients with delayed AOM initiation. HRs of both fractures were significantly greater in patients with a longer delay in AOM initiation (p value for trend<0.001). After excluding patients who had fractures before AOM initiation, the magnitude of HRs significantly decreased, and HR trends for hip fracture became insignificant., Conclusions: Delayed initiation of AOMs may result in increased fracture events, which may be reduced by early initiation of AOMs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy., Materials and Methods: We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group)., Results: Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group., Conclusion: Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality., (© 2022. The Japanese Society Bone and Mineral Research.)

Bone cement has been used in spinal surgery for as long as 50 years. In contemporary spinal surgery, cement augmentation of fractured osteoporotic vertebrae in the form of vertebroplasty/kyphoplasty as well as cement augmentation of pedicle screws in instrumented procedures of any etiology are established as standard procedures. Both procedures are very effective, although the benefits of vertebroplasty/kyphoplasty procedures have been controversially discussed in the past. Overall, complications rarely occur. The most relevant complication is cement leakage, which is asymptomatic in the majority of cases but in the worst case might lead to neurological deficits, embolic events and even circulatory collapse. Prevention of cement leakage is therefore crucial. Risk factors for cement leakage and preventive measures are presented in a comprehensive review based on the available literature., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: Clinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA., Methods: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7-12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids., Results: Among 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids., Conclusion: Clinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Comprehensive treatment for vertebral metastatic lesions commonly involves vertebral augmentation (vertebroplasty or kyphoplasty) to relieve pain and stabilize the spine followed by multiple sessions of radiotherapy. We propose to combine vertebral augmentation and radiotherapy into a single treatment by adding 32 P, a β -emitting radionuclide, to bone cement, thereby enabling spinal brachytherapy to be performed without irradiating the spinal cord. The goal of this study was to address key dosimetry and safety questions prior to performing extensive animal studies. The 32 P was in the form of hydroxyapatite powder activated by neutron bombardment in a nuclear reactor. We performed ex vivo dosimetry experiments to establish criteria for safe placement of the cement within the sheep vertebral body. In an in vivo study, we treated three control ewes and three experimental ewes with brachytherapy cement containing 2.23-3.03 mCi 32 P ml -1 to identify the preferred surgical approach, to determine if 32 P leaches from the cement and into the blood, urine, or feces, and to identify unexpected adverse effects. Our ex vivo experiments showed that cement with 4 mCi 32 P ml -1 could be safely implanted in the vertebral body if the cement surface is at least 4 mm from the spinal cord in sheep and 5 mm from the spinal cord in humans. In vivo , a lateral retroperitoneal surgical approach, ventral to the transverse processes, was identified as easy to perform while allowing a safe distance to the spinal cord. The blood, urine, and feces of the sheep did not contain detectable levels of 32 P, and the sheep did not experience any neurologic or other adverse effects from the brachytherapy cement. These results demonstrate, on a preliminary level, the relative safety of this brachytherapy cement and support additional development and testing., (© 2022 Institute of Physics and Engineering in Medicine.)

Objectives: To explore the influencing factors of bone cement leakage in the paravertebral vein after vertebroplasty for the treatment of osteoporotic vertebral compression fractures (OVCFs) and to determine the correlation between the puncture-side bone cement/vertebral body volume ratio and bone cement leakage in the paravertebral vein., Methods: This was a retrospective analysis of 495 patients (585 vertebral bodies) with OVCFs treated from August 2018 to May 2021 in our hospital. The patients' postoperative CT data were imported into Mimics software, and the three-dimensional(3D) reconstruction function was used to calculate the bone cement volume (BCV), puncture-side bone cement volume (PSBCV), and vertebral body volume (VBV); the bone cement/vertebral body volume ratio (BCV/VCV%) and puncture-side bone cement/vertebral body volume ratio (PSBCV/VCV%) were additionally calculated. Sex, Age, Body mass index(BMI), Bone density, BCV, PSBCV, VBV, BCV/VCV%, and PSBCV/VCV were compared between the leakage group and the non-leakage group. Logistic regression analysis was used to assess the correlations between the factors that statistically significantly differed between the two groups and the presence of leakage in the paravertebral veins. A receiver operating characteristic (ROC) curve was used to determine the diagnostic value of the PSBCV/VCV% and to obtain the optional cut-off value., Results: A total of 102 males and 393 females with an average age of 72.89 (52 ~ 93) years were included in our study. There were 57 cases of cement leakage (59 vertebral bodies) in the paravertebral vein. There were 438 patients (526 vertebral bodies) without paravertebral cement leakage. Univariate analysis showed that the differences in sex, bone density, PSBCV, and PSBCV/VCV% between the two groups were statistically significant (P < 0.05). Logistic regression analysis showed that there were correlations between sex, bone density, and PSBCV/VCV% and the presence of paravertebral cement leakage (P < 0.05). The ROC curve showed that the area under the curve of the PSBCV/VCV% for the diagnosis of cement leakage in the paravertebral vein was greater than 0.65, and P < 0.05, indicating a diagnostic value. The best cut-off point for the diagnosis of paravertebral cement leakage with the PSBCV/VCV% was 13.68%, with a sensitivity of 84.7% and specificity of 37.8%., Conclusion: Sex, bone density, and PSBCV/VCV% are risk factors for cement leakage in the paravertebral veins after vertebroplasty for the treatment of OVCFs; the PSBCV/VCV% is strongly associated with paravertebral venous leakage, and the optimal PSBCV/VCV% is 13.68%. When the PSBCV/VCV% exceeds the optimal value, the risk of cement leakage in the paravertebral vein becomes significantly increased., (© 2022. The Author(s).)

Bisphosphonates are commonly used in the treatment of osteoporosis. Long-term use without drug holiday causes the risk of atypical fractures. Subtrochanteric and femoral stress fractures are among the frequently described complications. In our case report; a stress fracture of the scapular spine, a previously undescribed adverse effect of bisphosphonates, is presented. Key words: bisphosphonates, scapular spine, stress fracture, drug holiday.

Vertebral fractures (VFs) are the most common type of osteoporotic fracture, and their prevalence and severity are key risk factors for future fragility fractures. Here, we assess the treatment effect of romosozumab on the incidence of new on-study VFs according to Genant severity grades (mild, moderate, and severe). Data are reported from two phase 3 clinical studies for patients who received romosozumab versus placebo through 12 months, followed by denosumab through 24 months (FRAME: NCT01575834), and for patients who received romosozumab through 12 months, followed by alendronate through 24 months, versus alendronate only through 24 months (ARCH: NCT01631214). The treatment effect of romosozumab is reported for all included patients, and for patients with prevalent and severe baseline VFs. The incidence of new moderate-or-severe VFs was reduced through 12 months for patients treated with romosozumab versus placebo (FRAME; 0.25% versus 1.42%, respectively; p < 0.001) or alendronate (ARCH; 2.78% versus 4.00%, respectively; p = 0.042). Furthermore, the treatment effect of romosozumab on the incidence of new VFs across moderate and severe severity grades was independent of baseline VF prevalence or severity; through 12 months, consistent reductions in new moderate-or-severe VFs were observed regardless of prevalent (FRAME; p = 0.18) or severe (ARCH; p = 0.52) VFs at baseline. Reductions in the incidence of new moderate and severe VFs were sustained through 24 months, after transition from romosozumab to denosumab or alendronate, independent of baseline VF prevalence or severity; no significant interactions were observed between the incidence of new moderate-or-severe VFs and the presence of prevalent (FRAME; p = 0.81) or severe (ARCH; p = 0.99) VFs at baseline. With increasing recommendations for initial treatment with bone-forming agents for postmenopausal women with osteoporosis, these analyses will help to inform treatment decisions for patients at very high risk of VF., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders., Objective: This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders., Methods: Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping., Results: A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9)., Conclusion: VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

People with epilepsy who take certain medications are at risk for developing osteoporosis and fractures of the vertebrae that commonly go undiagnosed. By using technology available in a bone density scan, we observed at least one fracture in many subjects with bone density in the normal and osteopenic range., Purpose/introduction: Chronic use of antiepileptic drugs (AEDs), both enzyme-inducing (phenytoin, phenobarbital, carbamazepine, and primidone) and non-enzyme-inducing (i.e., valproate), is recognized as a cause of secondary osteoporosis. Vertebral compression fractures (VF) are the most common type of osteoporotic fractures and may confer an increased risk of future hip, wrist, and vertebral fractures. Vertebral compression fractures in the general population are frequently asymptomatic, and under-diagnosed. The purpose of this study is to describe the prevalence of VF in a cohort of male veterans with epilepsy on chronic AEDs., Methods: The cohort for this study consisted of 146 male veterans who carried a diagnosis of epilepsy and were chronic users of AEDs known to cause osteoporosis (phenobarbital, phenytoin, carbamazepine, primidone, and valproate). Chronic AED use was defined as receiving an AED for at least 2 years. Subjects were previously seen in the osteoporosis clinic and had been evaluated by a dual-energy X-Ray absormetry (DXA) instrument including morphometric studies following a standard vertebral fracture assessment (VFA) protocol during the same DXA imaging acquisition session., Results: The mean age was 63 years. Low bone mineral density defined as osteoporosis or osteopenia was observed in 29% and 43% respectively. We observed at least one VF in 41 % of the subjects who had normal BMD, 54% in the osteopenic range, and 75% in the osteoporotic range., Conclusions: By performing a VFA in addition to standard bone densitometric studies, we disclosed a large prevalence of compression fractures in individuals with epilepsy chronically treated with AEDs who had BMDs in the normal and osteopenic ranges. The addition of VFA or other imaging methods to evaluate VF should be included in the evaluation of bone health in individuals with epilepsy receiving AEDs since it may modify treatment recommendations to prevent future osteoporotic fractures., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF)., Objective: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF)., Patients and Methods: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine., Results: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04)., Conclusions: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures., (© 2021 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Aim: To evaluate the ability of the trabecular bone score (TBS) to discriminate vertebral fracture (VF) and fragility fracture (FF) in patients with chronic inflammatory rheumatic diseases on long-term and low-dose glucocorticoid (GC) treatment and those without exposure to GC., Methods: This study assessed TBS and bone mineral density (BMD) in chronic GC users, defined as ≥2.5 mg/d of prednisone for >3 months (n = 89, mean age: 62.5 ± 11 years), and in controls (n = 59, mean age: 60.3 ± 9.6 years). Osteoporosis risk factors, radiographs of the thoracolumbar spine, non-VF history, osteoporosis drugs, and current/cumulative GC doses were collected. Patients were classified as high (TBS <1.23), intermediate (1.23-1.31), or low risk (>1.31), according to the fracture risk based on a recent meta-analysis., Results: The mean current dose and duration of GC treatment were 3.9 ± 1.9 mg/d and 3.9 ± 4.2 years, respectively. The prevalence of VF was significantly higher in chronic GC users than in controls (20.2% vs 5.1%, P = .010), although the prevalence of non-VF was similar (11.2% vs 5.1%). The GC group had significantly lower L1-L4 TBS and femur total BMD than did the controls (all with P < .01) without significantly different lumbar BMD. TBS (<1.31) showed a higher sensitivity for patients with VF and FF (83.3% and 81.8%, respectively) than with densitometric osteoporosis in the GC group (61.1% and 59.1%, respectively). Using the receiver operating characteristic curve, TBS <1.31 showed better diagnostic accuracy than TBS <1.23 and BMD in chronic GC users., Conclusion: TBS is more sensitive than BMD in detecting VF and FF in chronic GC users, even at a lower dose., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The authors present a rare case of multiple vertebral compression fractures in a young female with iatrogenic glucocorticoid-induced Cushing syndrome and concomitant human immunodeficiency virus (HIV) infection. Both long-term steroid use and HIV infection may lead to osteopenia or even osteoporosis. Multiple vertebral fractures in young patients are very uncommon and should alert the examiner to investigate any underlying cause. Treatment choices include pharmacological agents such as bisphosphonates or parathyroid hormone and even surgical interventions such as percutaneous vertebroplasty.

Background: What affects the efficacy of alendronate for prevention of glucocorticoid-induced (GI) fractures remains unclear. We aimed to explore the factors affecting alendronate's efficacy, and further identify subgroup effects of alendronate in preventing GI fractures., Methods: We searched 3 databases. Random-effects meta-analysis was conducted to synthesize risk ratio (RR) and 95% confidence interval (CI) for each endpoint. Meta-regression analysis was used to explore sources of heterogeneity, and subgroup analysis was used to address heterogeneity and evaluate subgroup effects. We detected publication bias using funnel plots and Egger tests., Results: We included 13 papers from 12 unique studies involving 46431 participants. Glucocorticoid (GC) dosage (P = .053) and proportion of previous vertebral fracture (PVF) (P = .047) were probably 2 sources of heterogeneity in meta-analysis for vertebral fractures, while GC duration (P = .020) was probably 1 for nonvertebral fractures. Alendronate reduced vertebral fractures in the high dosage subgroup (RR 0.61, 95% CI 0.44-0.86), but didn't in the low dosage subgroup (RR 1.56, 95% CI 0.20-12.02). Alendronate reduced vertebral fractures (RR 0.53, 95% CI 0.40-0.68) in the subgroup of PVF proportion <5%, but didn't (RR 0.76, 95% CI 0.42-1.37) in the subgroup of this proportion ≥5%. Alendronate reduced nonvertebral and hip fractures, whether in primary or in secondary prevention subgroup., Conclusions: The findings in our study support that alendronate is used for the primary and secondary prevention of GI fractures, but do not support that alendronate is recommended as a first-line agent for patients receiving a low dose of GCs or patients with PVF.

Background: Long-term glucocorticoid use increases fracture risk by reducing bone mass. This study evaluated the relationship between hip and vertebral fractures and the total amount of systematic glucocorticoid use., Methods: We randomly selected 1,896,159 people aged 20 to 100 years who participated in the National Health Checkup program in 2006. The amount of glucocorticoids prescribed was calculated based on the defined daily dose (DDD). The total DDD was obtained by adding oral and parenteral glucocorticoids for 6 months from the index date. Subjects were categorized into four groups according to total glucocorticoid DDDs: non-users (DDDs=0), low users (0&lt; DDDs ≤45), intermediate users (45&lt; DDDs ≤90), and high users (90&lt; DDDs). We followed them for 2 years. A multivariate Cox proportional hazard model was used to evaluate the effects of the total amount of glucocorticoid use on hip and vertebral fractures., Results: Higher glucocorticoid use was associated with a higher risk of vertebral fracture. Relative to non-users, the vertebral fracture risk was 1.39 times higher in the low-user group, 1.94 times higher in the intermediate-user group, and 2.43 times higher in the highuser group. The risk of hip fracture was 1.72 times higher in intermediate users and 3.28 times higher in high users than in non-users., Conclusion: As the amount of glucocorticoid use for 6 months increased, the risk of hip and vertebral fractures became higher. In order to prevent fractures, it is necessary for doctors to evaluate the total amount of glucocorticoid prescribed to the patient and to provide appropriate treatment.

Background: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures., Methods: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced., Results: A total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP., Conclusions: The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.

Here, we report the case of a 69-year-old female who discontinued denosumab to undergo dental treatment. She subsequently suffered rebound-associated vertebral fractures (RVFs) twice. Denosumab is approved in several countries for osteoporosis treatment. Its discontinuation can result in bone turnover rebound increase and rapid bone mineral density loss. Rebound-associated vertebral fractures (RVFs) after discontinuing denosumab have been widely reported. We previously reported the case of a patient who suffered RVFs after discontinuing denosumab to undergo dental treatment. A 69-year-old female suffered five acute VFs 10 months after the last denosumab injection. The current report identifies the risks associated with denosumab discontinuation to undergo dental treatment. The patient described in this report also underwent an additional clinical course after the first RVFs. Next month after the first RVFs, she developed severe back pain when she changed her posture. Magnetic resonance imaging showed new RVFs at T9 and T12 levels. This case indicates that RVFs may occur more than once. In addition, it suggests that additional denosumab injections do not completely eliminate the risk of RVFs.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Denosumab discontinuation is associated with a severe rebound effect combining elevation of bone remodeling markers for two years and loss of the gained bone density. In the absence of a potent bisphosphonate prescription at denosumab discontinuation, multiple vertebral fractures are frequent. The median number of vertebral fractures is 5, within 7 to 20 months (median 11) after the last denosumab injection. A potent bisphosphonate prescribed at denosumab discontinuation may reduce this risk. This strategy requires close monitoring of bone remodeling markers and adjustment of treatment if bone remodeling is not controlled., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Stroke is a major risk factor for osteoporosis and fractures. No study has evaluated the association between diuretic use and risk of vertebral fracture in stroke patients, although a considerable proportion of stroke patients are prescribed diuretics for hypertension. Our study aimed to investigate whether treatment with thiazides or loop diuretics affects the risk of vertebral fracture after stroke., Methods: A population-based propensity score-matched retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients with a new diagnosis of stroke between 2000 and 2011 were included. After propensity score matching, 9468 patients were included in the analysis of the effect of thiazides, of who 4734 received thiazides within 2 years after stroke. To analyze the loop diuretic effect, 4728 patients were included, of who 2364 received loop diuretics. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) of vertebral fractures among patients according to thiazide or loop diuretic use within 2 years following stroke. Sensitivity analyses based on the duration of thiazide or loop diuretic use were further conducted., Results: There was no significant difference in vertebral fracture risk between thiazide users and non-users (adjusted HR [aHR] = 1.14, 95% confidence interval [CI] = 0.88-1.47, p = 0.316). Loop diuretic users had a significantly higher vertebral fracture risk than non-users (aHR = 1.45, 95% CI = 1.06-1.98, p = 0.019). However, the sensitivity analysis revealed that short-term thiazide use (exposure duration < 90 days within 2 years after stroke) significantly increased the risk of vertebral fracture versus non-use (aHR = 1.38, 95% CI = 1.02-1.88, p = 0.039). Only short-term loop diuretic users had significantly higher risk of vertebral fracture (aHR = 1.56, 95% CI = 1.11-2.20, p = 0.011). The other two subgroups with longer exposure duration in analyses for both thiazides and loop diuretics revealed no significant effect., Conclusions: Short-term thiazide or loop diuretic use was associated with an increased risk of vertebral fracture after stroke. Further prospective clinical trials are required to confirm this finding.

Purpose of Review: Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it., Recent Findings: In the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple vertebral fractures is common or frequent (≥ 1/100 and < 1/10). In five recent case series, the median number of vertebral fractures was 5 within 7 to 20 months (median 11) after the last denosumab injection. Prescribing bisphosphonate before starting denosumab and/or after stopping denosumab may reduce this risk. However, only small case series have evaluated these strategies. After the second denosumab dose, there is a rebound effect with an increased risk of multiple vertebral fractures. A potent bisphosphonate prescribed at denosumab discontinuation could reduce this risk. As denosumab discontinuation is characterized by many uncertainties, denosumab is a second-line treatment for osteoporosis. Studies are urgently needed to define the management of denosumab discontinuation.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor for osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD patients, 35 current users of ICS and 26 who had never received glucocorticoids, were evaluated for bone mineral density (BMD) and body composition and underwent vertebral fracture assessment (VFA). The risk factors for bone disease considered for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the Brazilian population was also employed. The groups did not differ regarding gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score, prevalence of osteoporosis, or low BMD for age. Vertebral fractures were identified via VFA in seven patients using ICS and in none of those not receiving glucocorticoids (p = 0.02). There was a trend for an association between MMI and osteoporosis (p = 0.05) and for a progressive decrease in the BMD Z-score according to the COPD severity assessed via the GOLD score (p = 0.08). Vertebral fractures were not associated with osteoporosis (p = 0.69) or low MMI (p = 0.12). The fracture risk was not estimated by FRAX. ICS may lead to bone fragility before a significant decrease in BMD. Low muscle mass and COPD severity may contribute to bone disease.

Denosumab (DMAB) efficacy for treatment of osteoporosis was demonstrated in a pivotal trial with a reduction in vertebral and hip fractures during 3 years, and fracture risk reduction was sustained up to 10 years in an extension study. DMAB causes potent yet reversible inhibition of bone resorption. Bone density declines rapidly upon discontinuation and bone turnover markers increase above baseline in a rebound fashion. Spontaneous multiple vertebral fractures after DMAB discontinuation were recently reported. Prior treatment with bisphosphonates (BP) was postulated to decrease the risk for this alarming phenomenon. We aimed to describe our experience of fractures following DMAB withdrawal with special attention to past history of osteoporosis treatment. A phone survey of physicians engaged in bone metabolism from nine hospitals in Israel was performed. Clinical data of the patients presenting with vertebral fractures upon DMAB discontinuation were summarized and compared to the previously published cases. Nine elderly (74.2 ± 5.3 years) female patients were identified. Most patients had a prolonged prior exposure to BP (7.4 ± 3.2 years). All but one sustained osteoporotic fractures prior to DMAB initiation and their FRAX scores were high. Thirty-six vertebral fractures were identified in nine patients. Eight patients presented with multiple fractures, and most fractures were spontaneous. In line with the previous reports, the timing and severity of the fractures raise concern of DMAB discontinuation effect. Prolonged BP exposure in most of our patients challenges the protective effect hypothesis. Care providers, patients, and regulatory authorities should be aware of the possible risk of DMAB treatment interruption.

Multiple Vertebral Fractures after Denosumab Discontinuation: How to Avoid Them? Abstract. Denosumab is a monoclonal antibody raised against the RANK ligand that inhibits the maturation and activity of osteoclasts. It decreases bone resorption, increases bone density and reduces fracture risk. However, after its discontinuation, a significant rebound effect appears that lasts about two years. It results in increased markers of bone remodeling, a loss of bone density that may be greater than gain, and an increased risk of multiple vertebral fractures. These fractures occur at a frequency of 1 to 10 %. Due to this high risk, denosumab should be a second-line treatment limited to very specific indications. At denosumab discontinuation, in order to limit the rebound effect, the current recommendation is to prescribe a strong bisphosphonate (alendronate, zoledronate) and regularly monitor the bone resorption markers.

Denosumab is an effective treatment for osteoporosis. However, an increasing number of patients are developing so-called rebound vertebral fractures, because of a considerable increase of bone resorption after cessation of denosumab therapy. The prevalence of these new vertebral fractures is still unknown. In patients with high risk of new fractures, it is recommended to consider continuing denosumab treatment, or to switch to another antiresorptive medication such as bisphosphonates.

Pregnancy-related osteoporosis (PRO) is an uncommon metabolic bone disease that can result in vertebral fragility fractures. Here we report two cases of young women who had been previously treated with LMWH-enoxaparin and were diagnosed with PRO with vertebral fragility fractures after delivery. In first case report, a 33-year-old primigravid woman who was treated with 40 mg/day of enoxaparin for eight months to prevent venous thromboembolism was presented. After delivery, Dual energy X ray absorptiometry (DEXA) revealed osteoporosis in lumbar and femoral neck region. In magnetic resonance imaging (MRI), T4-T7 thoracic vertebral height losses were detected. In second case report, a 28-year-old primigravid woman which was treated with 40 mg/day enoxparin from the second month to the birth was presented. Osteoporosis in lumbar region was detected by DEXA. MRI revealed T12-L1 and L5 vertebral height losses. In conclusion, PRO can cause severe low back pain and should be considered in differential diagnosis. A detailed medical history should be essential to detect relationship between LMWH and PRO.

Objective: The aim of this paper is to review the available literature investigating the effect of epidural steroid injections (ESIs) on bone mineral density (BMD) and vertebral fracture risk., Study Design: Systematic review of current literature., Methods: The sources of the data were PubMed, Embase, Cochrane, and Scopus. Papers included in the review were original research articles in peer-reviewed journals., Results: A total of 7,233 patients (eight studies) with a mean age ranging between 49 and 74 years and an average follow-up between six and 60 months were studied. Steroids that were used included triamcinolone, dexamethasone, and methylprednisolone (MP), with a mean number of injections ranging from one to 14.7 and an average cumulative dose in MP equivalents between 80 and 8,130 mg. Epidural steroids were associated with significantly decreased BMD in four out of six included studies, and with increased risk of vertebral fracture in one out of two included studies. Significant reductions in BMD were associated with a cumulative MP dose of 200 mg over a one-year period and 400 mg over three years, but not in doses of less than 200 mg of MP equivalents for postmenopausal women and at least 3 g for healthy men. The risk of osteopenia and osteoporosis was lower in patients who were receiving anti-osteoporotic medication during the treatment course., Conclusions: ESIs should be recommended with caution, especially in patients at risk for osteoporotic fractures, such as women of postmenopausal age. Anti-osteoporotic medication might be considered prior to ESI.

Context: Bone loss and nonvertebral fractures have been reported in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid-stimulating hormone (TSH) suppressive therapy. Radiological vertebral fractures (VFs) are an early and clinically crucial marker of bone fragility., Objective and Design: A cross-sectional study to evaluate the prevalence and determinants of radiological VFs in women receiving l-thyroxine (L-T4) therapy for DTC., Patients and Interventions: A total of 179 consecutive women (median age, 59 years; n = 178 postmenopausal) who had undergone thyroidectomy for DTC and were currently receiving L-T4 were evaluated for radiological VFs and bone mineral density (BMD). There were three TSH target levels [<0.5 mU/L, group 1 (n = 83); 0.5 to 1.0 mU/L, group 2 (n = 50); >1.0 mU/L, group 3 (n = 46)]., Results: VFs were found in 51 patients (28.5%), with significantly (P < 0.001) higher prevalence in group 1 (44.6%) as compared with group 2 (24.0%) and group 3 (4.3%). VF prevalence was not significantly different among patients in group 1 with normal BMD, osteopenia, or osteoporosis, whereas in groups 2 and 3, VFs were more frequent in patients with osteoporosis than in those with either osteopenia or normal BMD. In the whole population, VFs were significantly and independently associated with TSH level <1.0 mU/L; densitometric diagnosis of osteoporosis at lumbar spine, femoral neck, or total hip; age of patients; and duration of L-T4 therapy., Conclusion: The prevalence of VFs was high in women with DTC who were undergoing long-term, suppressive L-T4 therapy.

The main pharmacovigilance updates in 2017 are reviewed. Denosumab : rebound-associated multiple vertebral fractures after discontinuation. Canagliflozine: increased risk of foot/leg amputations. Biologic and targeted cancer therapies, direct-acting antivirals for chronic hepatitis C: risk of hepatitis B reactivation. Checkpoint inhibitors : immune-related adverse events and graft rejection. Fingolimod : rebound-associated reactivation of MS following withdrawal. Daclizumab: risk of severe liver injury leading to restricted use in MS patients. Posaconazole: risk of overexposure when switching from oral suspension to tablets. Voriconazole: cutaneous squamous cell carcinoma under long-term therapy. Proton pump inhibitors : early exposure might increase fracture risk in young children., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

A considerable proportion of stroke survivors are prescribed with proton pump inhibitors (PPIs). Our study indicated that PPI use is associated with an increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke patients. The risk tends to increase as the cumulative doses of PPIs increase., Introduction: A considerable proportion of stroke survivors are prescribed with proton pump inhibitors (PPIs). Our study investigated the association between PPI use and the risk of osteoporosis and fracture among stroke survivors., Methods: A population-based propensity-matched retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients diagnosed with a new stroke between 2000 and 2012 were identified. After propensity score matching, 10,596 patients were enrolled, and 5298 patients were each assigned to the PPI user and non-user groups. Hazard ratios (HRs) were calculated for the risk of osteoporosis, hip fracture, and vertebral fractures according to PPI use or non-use. Sensitivity analyses were conducted to evaluate the dose effects of PPI., Results: PPI use after stroke was associated with an increased risk of osteoporosis, hip fracture, or vertebral fracture, with an adjusted HR (aHR) of 1.28 (P < 0.001). The aHRs were also significant for each outcome: osteoporosis, 1.26 (P < 0.001); hip fracture, 1.18 (P = 0.048); vertebral fracture, 1.33 (P < 0.001). A pattern of dose effect was identified. For any event (osteoporosis/hip fracture/vertebral fracture), the aHR for PPI use of 1-90, 91-365, and > 365 cDDDs was 1.22 (P < 0.001), 1.27 (P < 0.001), and 1.66 (P < 0.001), respectively. For each outcome, the highest dose was associated with the highest risk, with aHR of 1.79 (P < 0.001), 1.41 (P = 0.039), and 1.82 (P < 0.001) for osteoporosis, hip fracture, and vertebral fracture, respectively. Age- and sex-stratified analyses revealed similar patterns., Conclusions: PPI use is associated with an increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke patients.

Purpose of Review: The aim of this study is to summarize monitoring, prevention and treatment options of glucocorticoid-induced osteoporosis for patients on chronic glucocorticoid therapy., Recent Findings: Recent meta-analyses highlight the efficacy of bisphosphonate use in improving bone mineral density and in reducing vertebral fractures in the setting of long-term glucocorticoid use. A new study has now shown that alendronate also reduces the risk of hip fracture in glucocorticoid use. Emerging data indicate that teriparatide and denosumab also reduce the risk of osteoporotic fracture in glucocorticoid-induced osteoporosis., Summary: Glucocorticoid use is a leading cause of secondary osteoporosis; however, patients at risk of glucocorticoid-induced osteoporosis are often not evaluated or treated in a timely manner. Patients on a dose equivalent of 2.5 mg prednisone or greater for 3 months or longer duration should have their fracture risk assessed. Those at moderate or high risk should start bisphosphonate therapy, or if contraindicated, a second-line agent such as teriparatide or denosumab.

Teriparatide (TPTD) (recombinant DNA origin human parathormone [1-34]) is approved for the treatment of glucocorticoid-induced osteoporosis (GIO). There are reports of factors that affect the response to TPTD in GIO treatment. This work describes the case of a 71-yr-old woman diagnosed with lupus nephropathy treated with 40 mg/d of meprednisone, and who suffered multiple vertebral fractures. Despite treatment with a single 5 mg dose of zoledronic acid, the patient continued to have vertebral fractures. Treatment with 20 µg/d of subcutaneous TPTD (PTH1-34, Forteo; Eli Lilly Co., Indianapolis, IN) was initiated. Nine months after the onset of treatment, bone mineral density (BMD) assessment showed a 5% decrease in lumbar spine BMD. Factors potentially affecting the results were analyzed. The patient reported injecting TPTD at night and was instructed to inject TPTD in the morning before breakfast. After changing the time of TPTD administration and 22 mo after initiating treatment, BMD assessment was repeated and showed an 18% increase at the lumbar spine and no new vertebral fractures. The time of TPTD administration might affect the response to TPTD in GIO treatment., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear., Objective: In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels., Results: We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One-hundred-sixty-nine women were AI-naïve, and 94 were AI-treated. AI-treated patients had lower BMD at total hip (p=0.01) and lumbar spine (p=0.03), higher serum vitamin D (p<0.001) and parathyroid hormone (p=0.006) values as compared to AI-naïve patients. The prevalence of VFs was 18.9% in AI-naïve patients, and 31.2% in those assessed during AI therapy (odds ratio 1.90, 95% CI 1.1-3.5, p=0.03). In AI-naïve patients, VFs were associated with older age (p=0.002) and lower BMD values at femoral neck (p=0.04) and total hip (p=0.007), whereas VFs occurred without association with any parameter analyzed in AI-treated patients. In AI-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p=0.31)., Conclusions: In women with early BC, AI therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of AI-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with AIs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown., Objective: To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF., Design, Setting, and Participants: Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016., Exposures: Dabigatran or warfarin use during the study period., Main Outcomes and Measures: Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated., Results: Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 [95% CI, -0.38 to -0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 [95% CI, -2.40 to -3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, <.001)., Conclusions and Relevance: Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.

Introduction: Glucocorticoid therapy has a number of adverse effects, among which osteoporosis and bone fracture can be major complications. Immunosuppressive therapy for nephrotic syndrome is effective and can help to reduce the cumulative dose of glucocorticoids. Therefore, for this reason, the number of patients with nephrotic syndrome who develop glucocorticoid-related osteoporotic compression fracture is decreasing. Here we describe a pediatric case of multiple vertebral compression fractures due to glucocorticoid-induced osteoporosis during treatment for nephrotic syndrome., Case Presentation: A 12-year-old boy with nephrotic syndrome was treated with the standard corticosteroid regimen stipulated by the International Study of Kidney Disease in Children (ISKDC). Although he achieved complete remission, he suffered two episodes of relapse, and after the second such episode, the disease became resistant to the steroid therapy. Therefore, the patient received steroid pulse therapy followed by steroid tapering concomitant with cyclosporine administration. However, ~ 9 months after the start of steroid therapy, the patient developed multiple vertebral compression fractures with severe back pain., Conclusion: It is necessary to evaluate the state of bone at an early stage of treatment for nephrotic syndrome in children, even if the cumulative dose of glucocorticoid is not particularly high.
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Unlabelled: Efficacy of osteoporosis medication is not well-established among patients taking oral glucocorticoids. We assessed the efficacy of approved osteoporosis pharmacotherapies in preventing fracture by combining data from randomized controlled trials. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk., Introduction: Several osteoporosis drugs are approved for the prevention and treatment of glucocorticoid (GC)-induced osteoporosis. However, the efficacy of these treatments among oral GC users is still limited. We aimed to examine the comparative efficacy of osteoporosis treatments among oral GC users., Methods: We updated a systematic review through to March 2015 to identify all double-blinded randomized controlled trials (RCTs) that examined osteoporosis treatment among oral GC users. We used a network meta-analysis with informative priors to derive comparative risk ratios (RRs) and 95 % credible intervals (95 % CrI) for vertebral and non-vertebral fracture and mean differences in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD). Treatment ranking was estimated using the surface under the cumulative ranking curve (SUCRA) statistic. A meta-regression was completed to assess a subgroup effect between patients with prior GC exposures and GC initiators., Results: We identified 27 eligible RCTs examining nine active comparators. Etidronate (RR, 0.41; 95%CrI = 0.17-0.90), risedronate (RR = 0.30, 95%CrI = 0.14-0.61), and teriparatide (RR = 0.07, 95%CrI = 0.001-0.48) showed greater efficacy than placebo in preventing vertebral fractures; yet, no treatment effects were statistically significant in reducing non-vertebral fractures. Alendronate, risedronate, and etidronate increased LS BMD while alendronate and raloxifene increased FN BMD. In preventing vertebral fractures, teriparatide was ranked as the best treatment (SUCRA: 77 %), followed by risedronate (77 %) and zoledronic acid (76 %). For non-vertebral fractures, teriparatide also had the highest SUCRA (69 %), followed by risedronate (64 %). No subgroup effect was identified with regards to prior GC exposure., Conclusions: Despite weak trial evidence available for fracture prevention among GC users, we identified several drugs that are likely to prevent osteoporotic fracture. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk.