Osteoporotic fractures: an unrecognized adverse event of immune checkpoint inhibitors?

The widespread use of immune checkpoint inhibitors (ICIs) in clinical practice has broadened our understanding of their immune-related adverse events (irAEs). IrAEs, including musculoskeletal adverse events, remain a significant concern. While ICI-associated arthritis is a well-documented musculoskeletal side effect of ICI therapy, the direct effects of ICIs on bone in patients with cancer are poorly understood. There is emerging evidence to support the hypothesis that ICIs adversely impact bone turnover and can lead to osteoporosis and fragility fractures, which are not currently recognized as irAEs.

Osteoporotic fracture risk in women with breast cancer treated with aromatase inhibitors: a health insurance claims database study in Japan.

BACKGROUND: Hormone therapy with aromatase inhibitors (AIs) for estrogen receptor-dependent breast cancer may expose patients to an increased osteoporosis risk. This study was performed to estimate fracture risk in women with breast cancer to whom AIs were prescribed in Japan. METHODS: This retrospective study used data from the Japanese Medical Data Vision database. Women with breast cancer prescribed AIs over a 12-month period were identified and matched to women not prescribed AIs using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared using a cause-specific Cox hazard model. The proportion of women undergoing bone density tests was retrieved. RESULTS: For all fractures sites combined, cumulative fracture incidence at 10 years was 0.19 [95%CI: 0.16-0.22] in women prescribed AIs and 0.18 [95%CI: 0.15-0.21] without AIs. AI prescription was not associated with any changes in risk (adjusted hazard ratio: 1.08 [95%CI: 0.99-1.17] p = 0.08). Women prescribed AI more frequently underwent bone density testing (31.9% [95% CI: 31.2%; 32.6%] versus 2.2% [95% CI: 2.0%; 2.4%]). CONCLUSIONS: The anticipated association between AI exposure and osteoporotic fracture risk in Japanese women with breast cancer was not seen clearly.

Androgen deprivation therapy-related fracture risk in prostate cancer: an insurance claims database study in Japan.

INTRODUCTION: Androgen deprivation therapy (ADT) is widely used for the treatment of prostate cancer. ADT is associated with reduced bone density leading to an increased risk of osteoporotic fracture. The objective of this retrospective cohort study was to quantify fracture risk in men treated with ADT for prostate cancer in real-world practice in Japan. MATERIALS AND METHODS: Data were extracted from the Japanese Medical Data Vision (MDV) database. Men initiating ADT for treatment of prostate cancer between April 2010 and March 2021 were identified and matched to a cohort of prostate cancer patients not taking ADT using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared between cohorts using a Cox cause-specific hazard model. Information was extracted on demographics, comorbidities and bone densitometry. RESULTS: 30,561 men with PC starting ADT were matched to 30,561 men with prostate cancer not treated with ADT. Following ADT initiation, <5% of men underwent bone densitometry. Prescription of ADT was associated with an increased fracture risk compared to not taking ADT (adjusted hazard ratio: 1.63 [95% CI 1.52-1.75]). CONCLUSION: ADT is associated with a 1.6-fold increase in the risk of osteoporotic fracture in men with prostate cancer. Densitometry in this population is infrequent and monitoring urgently needs to be improved in order to implement effective fracture prevention.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

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.

Blood cadmium is associated with increased fracture risk in never-smokers - results from a case-control study using data from the Malmö Diet and Cancer cohort.

BACKGROUND: Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers. METHODS: The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression. RESULTS: Median B-Cd was 0.22 µg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per µg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 µg/L; OR 1.21; 95 % confidence interval 1.01-1.45). CONCLUSION: Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

Association between disease-modifying antirheumatic drugs and bone turnover biomarkers.

Rheumatoid arthritis (RA) has been linked to an increased risk of osteoporosis as well as fractures. Patients diagnosed with RA had a 25% increased risk of osteoporotic fracture, according to a recent population-based cohort study that compared them to people without RA. Several studies have found a correlation between osteoporosis and the presence of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and 6. These cytokines play a crucial part in the process of bone resorption by boosting osteoclast activation and encouraging osteoclast differentiation. Based on the correlation between RA, osteoporosis, and inflammation, it is possible that systemic immunosuppression with disease-modifying antirheumatic drugs (DMARDs) can help individuals with RA have a lower chance of developing osteoporosis and osteoporotic fractures. There is little information on how different DMARDs, biologic or non-biologic, affect RA patients' bone metabolism. In this study, we present an overview of the influence that targeted therapies, such as biologics, non-biologics, and small molecule inhibitors, have on bone homeostasis in RA patients.

Real-world use of bone modifying agents in metastatic, castration-resistant prostate cancer.

BACKGROUND: Bone modifying agents (BMAs) prevent skeletal related events among patients with metastatic, castration-resistant prostate cancer (mCRPC) involving bone and prevent osteoporotic fractures among patients at high risk. BMA utilization for patients with mCRPC has not been well quantified. METHODS: We used linked SEER registry and Medicare claims data. We included men diagnosed with stage IV prostate adenocarcinoma during 2007-2015, aged > = 66 at diagnosis, with sufficient continuous enrollment in Medicare Parts A, B, and D, who received androgen deprivation therapy. We limited to those who subsequently received a CRPC-defining treatment (CDT). We identified patients with evidence of bone metastasis using claims. Our primary outcome was receipt of a BMA (zoledronic acid or denosumab) within 180 days of initiating CDT. RESULTS: Among 1292 included patients, 1034 (80%) had bone metastasis. BMA use within 180 days of initiating CDT was higher among patients with bone metastases than those without (705/1034 [68%] vs 56/258 [22%]). Among patients without bone metastasis, those with high osteoporotic fracture risk were more likely than those without to receive a BMA (OR = 2.48, 95% CI: 1.17, 5.29); however, only 26% of patients with high fracture risk received a BMA. Among patients who received BMAs, most (62%) first initiated them >90 days before initiating CDT. CONCLUSIONS: Two-thirds of patients with mCRPC and bone metastases received BMAs within 180 days after initiating CDT. A greater proportion of patients without bone metastasis may warrant BMA therapy for osteoporotic fracture prevention. Some patients with bone metastasis may be able to delay BMA initiation until CRPC.

A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting.

PURPOSE: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. METHODS: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. RESULTS: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37). CONCLUSIONS: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy. IMPLICATIONS FOR CANCER SURVIVORS: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.

Improving bone health in prostate cancer patients starting androgen deprivation therapy: does Fracture Risk Assessment Tool (FRAX®) enhance stratification and targeted management?

Androgen deprivation therapy for prostate cancer can lead to osteoporosis and increased fracture risk. The Fracture Risk Assessment Tool (FRAX®) questionnaire can be used for risk stratification, and our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture. PURPOSE/INTRODUCTION: Long-term use of androgen deprivation therapy (ADT) in prostate cancer patients results in increased bone turnover and decreased bone mineral density (BMD). Proper assessment of any existing osteoporotic fracture risk is crucial prior to starting treatment. However, this risk assessment is poorly performed in these patients in spite of available validated tools including the Fracture Risk Assessment Tool (FRAX®). The objective of this study was to assess the distribution of osteoporotic fracture risk in a cohort of men commencing ADT for prostate cancer using the FRAX® algorithm. METHODS: Between July 2020 and May 2022, 200 men filled in the FRAX® questionnaire just before ADT. They were stratified into the high-risk (> 20% probability of a MOF over the next 10 years), intermediate-, and low-risk categories for fragility fractures. We also measured their serum vitamin D and calcium levels. RESULTS: The average age was 73.5 years (54-89). It took less than 10 min to complete the assessment. Only six patients were at high-risk, were started on bisphosphonates immediately, and referred for a dual energy X-ray absorptiometry (DEXA) scan. Twelve patients in the intermediate-risk category were referred for DEXA scans for bone mineral density measurements. A total of 182 patients (91%), were in the low-risk category and given lifestyle advice only. All had normal calcium levels but 134 (67%) patients, mostly in the low-risk category, had reduced vitamin D levels (< 50 nmol/L). CONCLUSION: The FRAX® questionnaire is simple and immediately identifies patients who are at risk of fragility fractures. Our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture. We were surprised that more than half of our patients had low vitamin D levels.

Application and prospect of trabecular bone score in differentiated thyroid cancer patients receiving thyrotropin suppression therapy.

Thyroid-stimulating hormone (TSH) suppression therapy is one of the common treatments for most patients with differentiated thyroid cancer (DTC). Unfortunately, its detrimental effects on bone health are receiving increasing attention. It may increase the risk of osteoporosis and osteoporotic fractures. The trabecular bone score (TBS) is a relatively new gray-scale texture measurement parameter that reflects bone microarchitecture and bone strength and has been shown to independently predict fracture risk. We reviewed for the first time the scientific literature on the use of TBS in DTC patients on TSH suppression therapy and aim to analyze and compare the utility of TBS with bone mass strength (BMD) in the management of skeletal health and prediction of fracture risk. We screened a total of seven relevant publications, four of which were for postmenopausal female patients and three for all female patients. Overall, postmenopausal female patients with DTC had lower TBS and a significant reduction in TBS after receiving TSH suppression therapy, but their BMD did not appear to change significantly. In addition, TBS was also found to be an independent predictor of osteoporotic fracture risk in postmenopausal women with DTC receiving TSH suppression therapy. However, due to limitations in the number of studies and study populations, this evidence is not sufficient to fully demonstrate the adverse effects of TSH suppression therapy on patients' TBS or BMD and the efficacy of TBS, and subsequent larger and more case-cohort studies are needed to further investigate the relationship and application of TBS to TSH suppression therapy in terms of skeletal health impairment and fracture risk in DTC patients.

Low vertebral CT Hounsfield units: a risk factor for new osteoporotic vertebral fractures after the treatment of percutaneous kyphoplasty.

PURPOSES: To identify the characteristics of the vertebral HU in the elderly patient with new osteoporosis vertebral compression fractures (OVCF) after treatment of percutaneous kyphoplasty (PKP), which may help us to preliminarily evaluate the risk of a new OVCF after the treatment of PKP. METHODS: We retrospectively analyzed the patients who received PKP treatments in our hospital to find out the patients suffered new OVCFs after the treatment of PKP and set an age-, sex-, first fracture vertebrae-, surgical segment-, and comorbidity-matched control group without new fractures. We measured the axial and sagittal L1-HU values to compare their differences. RESULTS: There were 32 patients who suffered new OVCFs and received another PKP surgery in our department. In the study group, the average L1 sagittal and axial HU values were 46.17 ± 21.31 HU and 47.77 ± 22.38 HU, and they had no statistical difference (P > 0.05). For the control group, the average L1 sagittal and axial HU values were 75.69 ± 29.72 HU and 80.23 ± 30.26 HU, and their difference was not significant (P > 0.05). No matter from the axial or sagittal evaluation, the L1 HU value in the study group was significantly lower than that in the control group (P < 0.001). The AUC of using the L1 axial HU value to differentiate patients with new fractures from controls was 0.85 while the sagittal one was 0.82. In axial (and sagittal) evaluation, the cutoff value (adjusted to the multiple of five) had high specificity of 90% or high sensitivity of 90% to identify patients with new fractures of 45 HU and 75 HU (50 HU and 75 HU), respectively. CONCLUSIONS: The lower the vertebral HU value is, the more likely the patients suffer new OVCFs after PKP treatment.

The Effects of Bone Cement Volume in Percutaneous Vertebroplasty for Thoracolumbar Junction Vertebral Compression Fractures: A Clinical Comparative Study.

We compared the outcomes of patients treated with different volumes of polymethyl methacrylate bone cement during percutaneous vertebroplasty (PVP) for thoracolumbar vertebral compression fractures. We performed a comparative, retrospective study of 316 patients who underwent PVP for a single-level thoracolumbar vertebral compression fracture. Patients were divided into two groups: group A (≤5 mL; n = 146) and group B (>5 mL; n = 170). The visual analogue scale (VAS) for pain and the Roland-Morris Disability Questionnaire (RDQ) scores were compared between the two groups at 1 week and at 1, 6, 12, and 24 months after PVP. The incidence of cement leakage into the intervertebral discs was evaluated by a postoperative lateral radiograph assessment. Patients were evaluated for new fractures 1 and 2 years after PVP or when new fractures were suspected. Among the 316 patients enrolled, 245 completed the clinical research. No difference between groups A and B in terms of the VAS, RDQ, and rate of complications at all time points after surgery was observed. The presence of intervertebral disc leakage was a relative risk (RR) for subsequent total vertebral fracture (RR, 6.42; 95% confidence interval (CI), 2.72-14.19; P < 0.0001) and adjacent vertebral fracture (RR, 8.03; 95% CI, 2.74-23.54; P = 0.0001). A high volume of bone cement may increase the rate of subsequent total and adjacent vertebral fractures. However, the occurrence of intervertebral disc leakage is the principal risk factor for these negative outcomes of PVP.

The effects of biomechanical factors on adjacent vertebral compression fractures after percutaneous kyphoplasty: a propensity score matching analysis.

Adjacent vertebral compression fracture (AVCF) is the primary factor affecting satisfaction after PKP surgery. In addition to osteoporosis, certain structural characteristics of the vertebral body itself also increase their risk. The purpose of this study was to explore the impact of biomechanical changes on AVCF after balancing other factors. INTRODUCTION: As a routine treatment of OVCF, the postoperative refracture of PKP is a serious problem. The aim of our study was to explore the impact of lumbar biomechanical changes on the risk of AVCF. A propensity score matching was performed to balance the interference of osteoporosis, which is the primary risk factor of AVCF. METHODS: A retrospective, single-center case-control study was performed. From September 2013 to March 2020, 1752 patients were enrolled, and AVCF was assessed in 80 of these patients. A propensity score matching (PSM) analysis was performed, and 5 potential confounding factors were matched (age, BMI, number of fractured vertebral bodies, fracture region, and HDL). The preoperative and postoperative radiological factors were measured in the matched cohort of 48 pairs. A conditional logistic regression analysis to adjust the comparative risks. RESULTS: The preoperative wedge angle and its postoperative recovery of the AVCF group were significantly higher than that of the non-AVCF group. The local kyphosis of the fractured vertebral body between the two groups was similar, but the recovery in the AVCF group was slightly higher than that in the non-AVCF group. The preoperative and postoperative relative anterior height (RAH) of the fractured vertebral body was familiar in two groups, so was the recovery of RAH. The preoperative spino-sacral angle (SSA) was significantly higher in the AVCF group than in the non-AVCF group. The preoperative wedge angle was identified as the only significant risk factor for AVCF in the multivariate analysis. CONCLUSION: In conclusion, a larger preoperative fracture vertebral wedge angle is a risk factor for AVCF. For such high-risk patients, surgeons should be cautious about surgical decisions. The postoperative active measures and tailored surveillance should be attached to great importance as well.

The use of oral glucocorticoids and the risk of major osteoporotic fracture in patients with myasthenia gravis.

Oral glucocorticoids may increase major osteoporotic fracture risk (MOF) in myasthenia gravis patients. To assess this risk, we performed a case-control study including all Danish patients with a MOF between 1995 and 2011. We also pooled our data with data from another study. We found no increased risk. Osteoporosis prevention remains advisable. PURPOSE/INTRODUCTION: The prolonged use of high doses of oral glucocorticoids (GCs), a common treatment in patients with myasthenia gravis (MG), may increase major osteoporotic fracture (MOF) risk. Previous epidemiological studies did not exclusively focus on patients with MG or had relatively few GC-exposed MG patients. Aims were to evaluate the risk of MOF in MG patients using oral GCs in a large study population and to perform a pooled analysis with data from previous work. METHODS: A population-based case-control study (1995-2011) was conducted using the Danish National Health Service. Cases had sustained a MOF, and controls had not. All were aged ≥ 18 years. Multivariate conditional logistic regression estimated odds ratios (ORs) among MG patients using oral GCs versus non-users. Adjustments were made for comorbidities and comedications. In the pooled analysis, results were pooled by the use of generic inverse variance methods, assuming a random-effects model. RESULTS: We identified 376,858 cases and 376,858 controls. MOF risk was not elevated in MG patients currently using oral GCs compared to MG patients not on oral GCs (ORadj.: 1.26 (95% CI 0.68-2.33)). The use of the highest cumulative dose of oral GCs (≥ 7 g) did not show an increased risk of MOF among MG patients (ORadj.: 2.00 (95% CI 0.90-4.44)). Our pooled analysis also showed no association between oral GC use and MOF risk. CONCLUSION: This study showed that oral GC use in patients with MG was not associated with increased risk of MOF in our case-control study and pooled analysis. Osteoporosis prevention in MG patients based on clinical guidelines remains advisable.

The association between endocrine therapy use and osteoporotic fracture among post-menopausal women treated for early-stage breast cancer in Ontario, Canada.

BACKGROUND: The use of endocrine therapy for early-stage breast cancer, particularly aromatase inhibitor therapy has been associated with an increased risk of osteoporosis and fracture in clinical trials. We sought to validate this observation in real-world practice. METHODS: We used health administrative data collected from post-menopausal women (aged ≥66 years) who were diagnosed with breast cancer and started on adjuvant endocrine therapy from 2005 to 2012. Patients were classified by use of either an aromatase inhibitor or tamoxifen and followed until 2017 for a new diagnosis of an osteoporotic fracture. A multivariable analysis using a Cox proportional hazards model was adjusting for age, medical co-morbidities, medication use and duration of endocrine therapy. RESULTS: We identified 12,077 patients of whom 73% were treated with an aromatase inhibitor as compared to 27% with tamoxifen. Our multivariable analysis did not demonstrate any significant difference in the rate of osteoporotic fracture between patients treated with an aromatase inhibitor when compared with tamoxifen [Hazard ratio (HR) = 1.09; 95% confidence interval (CI) = 0.96-1.23, p-value = 0.18]. The 5-year rate of osteoporotic fracture for patients treated with either an aromatase inhibitor or tamoxifen was 7.5% and 6.9%, respectively. A completed sensitivity analysis did observe a decreased risk of fracture associated with tamoxifen usage over time. CONCLUSION: We could not detect a significant difference in the rate of osteoporotic fracture among patients treated with an aromatase inhibitor versus tamoxifen. Nonetheless, the risk with tamoxifen was numerically lower and significantly decreased when accounting for total duration of endocrine therapy.

Evaluation of care delivery by a novel multidisciplinary bone health clinic for patients at risk of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) is a common condition associated with increased risk for fracture. Many patients receive suboptimal care. We created a novel GIOP clinic model which successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. INTRODUCTION: This study characterizes the patient population referred to our novel glucocorticoid-induced osteoporosis (GIOP) clinic and evaluates how well the clinic performed in addressing key components of GIOP preventive care. METHODS: This population-based prospective cohort study derives data from patients reviewed at the University of Alberta Multidisciplinary Bone Health Clinic from January 2017 to September 2019. To create our clinic model, key components of GIOP preventive care were summarized based on current guidelines, and clear responsibilities were delegated to each multidisciplinary team member. A REDCap database was constructed, and each patient's multidisciplinary assessment was entered at each visit. Demographic and treatment data was extracted from our database. RESULTS: The clinic was able to achieve optimal GIOP preventive care in 60.1% of patients and in 78.7% of patients when excluding wait time. Of the 245 GIOP patients assessed, over half were females (56.7%) and the mean age was 56.7 years (range 16-95 years). Referrals were primarily made by specialists. Low-trauma fractures were reported in 24.9% of patients and 95.5% of patients had a baseline dual-energy X-ray absorptiometry (DXA). The mean current daily prednisone-equivalent dose was 14.1 mg. All patients received a recommendation for pharmacotherapy (100%) and the majority received counseling on vitamin D (98.8%), calcium (97.8%), smoking cessation (98.8%), alcohol reduction (98.4%), falls prevention (88.6%), and exercise (85.3%). CONCLUSION: Our novel GIOP clinic model successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. Further studies are required to assess the real-world long-term outcomes of our model.