Multiple Vertebral Fractures Research Articles

Clinical experience with denosumab discontinuation.

Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures. We wanted to examine if the recommendation stated in the ECTS position paper on DMAb discontinuation can prevent the bone loss in a clinical setting. We conducted a retrospective cohort study based on medical records of patients referred for DMAb discontinuation. We administered zoledronate (ZOL) 6 months after the last DMAb injection and 3, 6, 12, and 24 months thereafter if p-C-terminal collagen crosslinks (CTX) increased above 0.5 μg/l or BMD decreased (≥ 5% at the hip, ≥ 3% at the spine) at months 12 and 24. We included 66 women and men discontinuing DMAb after a mean treatment duration of 6.7 ± 2.7 (mean ± SD) years. BMD decreased 12 months after the initial ZOL treatment by 2.5 ± 4.2% and 1.9 ± 2.5% at the LS and TH, respectively (n = 44) (p ≤ 0.001 for all). There was no significant change in FNBMD (0.0 ± 5.1) (p > 0.05). No significant change in BMD was seen from month 12 to month 24 at any site (p > 0.05 for all). Thirty percent and twenty-two percent of patients experienced flu-like symptoms after the first and second ZOL infusion. No fractures occurred during the study period. Adhering to the recommendation in the ECTS position statement, a mean of 3 infusions of ZOL limited the bone loss 12 and 24 months after DMAb discontinuation, thereby preserving most of the BMD gained during DMAb treatment. The frequent occurrence of flu-like symptoms after ZOL proves to be a challenge, showing that routine prophylaxis against acute phase responses should be considered in patients treated with ZOL after discontinuing DMAb.

Similarities in distribution pattern between acute multiple osteoporotic vertebral compression fractures and vertebral fractures cascades

BackgroudOsteoporotic vertebral compression fractures (OVCF) cascades (OVCFcs) repeatedly cause vertebral compression to involve multiple vertebra. This study aimed to introduce an accelerated form of OVCFcs: acute multiple OVCF (amOVCF).MethodsOVCF patients with multiple vertebral augmentations in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, spine trauma, anatomical distribution, and distribution pattern of OVCF in OVCFcs and amOVCF were summarized and compared.Results429 patients with multiple vertebral augmentations in 1164 vertebra were included. There were 210 OVCFcs accumulating 622 OVCF and 219 amOVCF simultaneously involving 542 vertebra. The OVCFcs progressed at 0.48 fractures and 0.56 vertebra per year. Both OVCFcs and amOVCF demonstrated asymmetrical bimodal distribution in spine and most frequently involved L1. The incidence of adjacent OVCF was 40.14% in amOVCF with 2 OVCF and 84.72% in amOVCF with ≥ 3 OVCF, and the distribution pattern of OVCF was not significantly different between amOVCF and OVCFcs. The female/male ratio was 5.56 in OVCFcs and not different from that of 4.34 in amOVCF. The age of females (73.41 ± 8.08 and 76.29 ± 8.25 years old) but not males (77.20 ± 10.13 and 79.75 ± 10.21 years old) was significantly increased from initial to last OVCF in OVCFcs. amOVCF had similar age (72.26 ± 10.09 years old) as OVCFcs at initial OVCF (73.99 ± 8.51 years old) and were significantly younger than OVCFcs at last OVCF (76.82 ± 8.64 years old). 54.29% in OVCFcs and 48.4% in amOVCF reported no evident trauma, and the ratio of apparent spine trauma was higher in amOVCF (43.38%) than in OVCFcs (28.54%).ConclusionsamOVCF are accelerated form of OVCFcs showing similar anatomical distribution and distribution pattern of OVCF in spine. Both amOVCF and OVCFcs cause multiple fragility fractures without significant spine trauma.

A Case of Multiple Vertebral Fractures Caused by Glucocorticoid-induced Osteoporosis in a Pregnant Woman with Systemic Lupus Erythematosus

A Case of Multiple Vertebral Fractures Caused by Glucocorticoid-induced Osteoporosis in a Pregnant Woman with Systemic Lupus Erythematosus

Hyperparathyroidism in Patients with End-Stage Chronic Liver Disease (Clinical Observations)

Aim: to present disorders of mineral and bone metabolism in patients with chronic liver diseases through clinical observations.Key points. The liver plays an important role in mineral metabolism: metabolic activation of vitamin D, synthesis of vitamin D-binding protein and albumin, metabolism of parathyroid hormone, etc. However, data on the development of mineral metabolism disorders, particularly hyperparathyroidism, in this population are very limited. Bone diseases such as osteoporosis and osteomalacia are quite common in chronic liver disease, especially in cirrhosis and cholestatic diseases; however, the pathogenesis of these disorders and their relationship with mineral metabolism remain poorly understood. The article presents cases of severe primary hyperparathyroidism (PHPT) in patients with chronic liver disease. In one patient with a long history of viral hepatitis C and cirrhosis, PHPT manifested with severe bone complications, including multiple vertebral compression fractures and a subsequent femoral neck fracture. Imaging studies revealed lesions of all four parathyroid glands, and the removal of the largest lesion did not result in disease remission. In the second case described, PHPT was diagnosed in a patient with bone pain and osteoporosis following orthotopic liver transplantation for Budd — Chiari syndrome with cirrhosis. One year after the initial surgical treatment for PHPT, the patient experienced a recurrence of the disease, with confirmed multiglandular lesion.Conclusion. In patients with chronic liver diseases, disorders of mineral and bone metabolism remain a significant yet not fully understood problem. Further studies are needed to develop therapeutic approaches for this group of patients to prevent the onset of late, disabling complications.

Fracture severity dependence of bone and muscle performance in patients following single or multiple vertebral fractures.

Few studies focus on the clinical, laboratory, radiological, and biological characteristics of bone and muscle of multiple vertebral fractures, which are associated with a more poor prognosis compared with single fracture. To compare the BMD, bone turnover, muscularity, fatty infiltration of muscle, and prevalence of co-morbidities in patients with single and multiple vertebral fractures. We recruited 100 patients with single fracture (age 66.96 ± 8.24 years) and 100 with multiple fractures (age 69.90 ± 7.80 years); performed dual-energy X-ray absorptiometry of the femoral neck, hip, and lumbar vertebrae; and measured biochemical markers of bone turnover, muscularity, and fatty infiltration. Patients with multiple vertebral fractures had lower hip BMD (p=0.010) than those with single fractures, but there was no difference in femoral neck and lumbar vertebral BMD nor in muscularity. However, fatty infiltration, an indicator of muscle quality, was significantly higher in participants with multiple fractures (p=0.006). Diabetes was significantly more common in patients with multiple fractures (p=0.042). There were no significant differences in markers of bone turnover, and Seperman analyses showed no correlations of CTX-1 or tPINP with the BMD of the hip, femoral neck, or lumbar spine. However, high CTX-1 was associated with high tPINP (r=0.4805; p<0.0001), and marked fatty infiltration was associated with low hip, lumbar vertebral, and femoral neck BMD. Cox regression analyses showed that age (OR 1.057; 95% CI 1.016-1.101; p=0.006) and low hip BMD (OR 0.016; 95% CI, 0.000-0.549; p=0.022) were associated with a higher risk of multiple fractures. Patients with multiple fractures tend to have lower hip BMD, a history of type 2 diabetes, and more substantial fatty infiltration of muscle than in those with single fractures. Age and hip BMD rather than lumbar vertebrae BMD were found to be independent risk factors for multiple vertebral compression fractures, implying that hip BMD may be a more sensitive predictor for multiple vertebral fractures. More improvements in hip BMD and focus on older persons may be useful means of preventing multiple fractures.

Assessment of trabecular bone score (TBS) in the prediction of vertebral fracture in postmenopausal osteoporosis

The study aimed to evaluate the role of trabecular bone score (TBS) as determinant in the risk for vertebral fracture (VF) and define specific TBS threshold/s in women with postmenopausal osteoporosis.We studied 107 women with postmenopausal osteoporosis characterized by L1-L4 T-score ≤ −3.0 with (group 1) and without (group 2) VF, or L1-L4 T-score ≤ −1.0 and ≥ −2.4 and multiple vertebral fractures (VF) (group 3). We assessed 30 postmenopausal women with L1-L4 T-score ≤ −1.0 and ≥ −2.4 and no VF as controls (group 4). We measured L1-L4, femoral neck and total hip areal bone mineral density (aBMD) by dual X-ray absorptiometry (DXA) (QDR 4500; Hologic, Waltham, MA) and calculated TBS from de-identified DXA L1-L4 scans by the TBS iNsight software (Medimaps, Geneva, Switzerland). The assessment of VF was performed by means of anteroposterior and left lateral standardized radiographs of the thoracic and lumbar spine. We calculated the FRAX® value in all subjects for the assessment of 10-year fracture risk for major and hip fractures.Forty-two subjects with L1-L4 T-score ≤ −3.0 had at least one VF (group 1), while 41 have no VF (group 2). Twenty-four subjects had L1-L4 T-score ≤ −1.0 and ≥ −2.4 and at least 3 VF (group 3). We observed significantly lower TBS values in group 1 and group 3 compared to group 2 (p < 0.001) and group 4 (p < 0.05). L1-L4 aBMD and TBS values were not significantly associated in all groups. Interestingly, TBS values were independently associated with the presence of VF (log odds ratio − 8, p < 0.001) but not with the number of VF by the stepwise regression analysis. Furthermore, when we applied the cut-off value of TBS associated with degraded microarchitecture and elevated fracture risk (< 1.23), only 52 % of the subjects had VF. The cut-off value of TBS below which VF could be predicted was calculated by the receiver operating characteristic curve analysis and was 1.13.Our study demonstrates an independent association between altered trabecular microarchitecture, assessed by TBS, and the occurrence of VF in postmenopausal women with osteoporosis. This association is significant for values of TBS lower than those reported by population-based studies. Cut-off values of TBS need further evaluation by specifically designed studies assessing disease- specific thresholds for fracture risk.

Risk Factors for Adjacent Vertebral Fractures Following Cement Vertebroplasty: The Clinical Significance of Multiple Preexisting Vertebral Compression Fractures.

A retrospective cohort study. The study retrospectively analyzed the factors associated with the development of adjacent vertebral fractures. Adjacent vertebral fractures (AVF) may occur following cement vertebroplasty, and several risk factors have been reported with controversies. A total of 123 patients, with a mean age of 79.2 years, who underwent single-level vertebroplasty were included in the investigation. We systematically collected data encompassing baseline demographics, osteoporosis parameters, surgical details, radiologic measurements, and Hounsfield unit (HU) values in the lumbar spine. Subsequently, univariable, followed by multivariable logistic regression analyses, were employed to identify the risk factors of AVFs. Thirty of 123 patients had AVFs within 6 months following vertebroplasty. The AVF group exhibited a higher percentage of multiple preexisting vertebral compression fractures (P=0.006), a greater volume of injected cement (P=0.032), and a more pronounced reduction in local kyphosis (P=0.007). Multivariable logistic regression analysis revealed multiple preexisting vertebral compression fractures and a reduction in local kyphosis exceeding 8 degrees were independent risk factors for AVFs (P=0.008 and 0.003, respectively), with odds ratios of 3.78 (95% confidence interval: 1.41-10.12) and 4.16 (95% CI: 1.65-10.50), respectively. Subgroup analysis showed that patients with multiple preexisting vertebral compression fractures (VCFs) had significantly lower bone mineral density Z-score, T-score, and HU values compared with those without preexisting VCFs (P<0.05). Conversely, there were no significant differences in T-score or HU values between patients with no VCFs and those with a single VCF. This study demonstrated that both bone strength and local alignment are key factors associated with adjacent vertebral fractures. Specifically, having multiple preexisting vertebral compression fractures and a reduction in local kyphosis exceeding 8 degrees are independent risk factors. The presence of more than one previous vertebral compression fracture serves as a significant clinical indicator of advanced bone density reduction in patients with osteoporosis, offering a quick and straightforward method for identifying high-risk patients. Patients exhibiting these risk factors should be monitored more closely for favorable clinical outcomes. Level III-retrospective nonexperimental study.

8136 Using High-Resolution Peripheral Quantitative Computed Tomography to Assess Bone Microarchitecture and Guide Osteoporosis Treatment

Abstract Disclosure: S.V. Rupani: None. J. Sfeir: None. L. Graeff-Armas: None. Bone microarchitecture is an important factor that impacts bone strength. Unlike other factors that affect bone strength, such as bone mineral density and bone turnover, assessment of bone microarchitecture is not yet widely accessible in clinical practice. Computed tomography is the primary method of non-invasively assessing bone microarchitecture. High-resolution peripheral quantitative CT (HR-pQCT) is an emerging imaging modality that provides a three-dimensional assessment of bone densitometry, morphometry, and microarchitecture with a low effective radiation dose. It provides a quantitative and qualitative assessment of cortical and trabecular structural and mechanical properties. We present two similar cases of osteoporosis in males, where knowledge of bone microarchitecture through HR-pQCT helped formulate two distinct and targeted therapeutic approaches. The first case is of a 46-year-old male with a history of idiopathic osteoporosis with multiple nontraumatic vertebral fractures. Given his presentation and age, anabolic therapy such as teriparatide was being considered. He underwent HR-pQCT scanning, which showed average radial trabecular parameters, but his cortical porosity was significantly above average, with similar findings in his tibial parameters. Since teriparatide has been shown to increase cortical porosity, this would not be the best option for our patient, given the risk of further weakening of the microarchitecture of his cortical bone. Therefore, denosumab, which has been shown to decrease cortical porosity, was chosen. Our second patient is a 52-year-old male with idiopathic osteoporosis with multiple nontraumatic vertebral fractures, whose HR-pQCT showed average cortical parameters at both the radius and tibia but low trabecular number and increased trabecular separation at both sites. Since teriparatide increases trabecular thickness and mass, we could confidently choose teriparatide for this patient, with less concern for significant deleterious effects on his cortical bone parameters. These case reports highlight the impact that the assessment of qualitative properties of bone, such as microarchitecture, can have in the management of osteoporosis. Currently, the lack of sufficient validated normative data for HR-pQCT limits its widespread use in the diagnosis of osteoporosis and fracture prediction. However, given that HR-pQCT can characterize the properties of trabecular and cortical bone, it may have a role in helping guide osteoporosis treatment, especially in challenging and atypical cases. Presentation: 6/3/2024

7635 Severe Osteoporosis in a Patient with Heterotopic Calcification: A Case Report

Abstract Disclosure: D. Salih Bacha: None. L.Z. Khan: None. Background: While osteoporosis and heterotopic ossification (HO) are distinct conditions affecting bone health, their coexistence poses intriguing clinical challenges. Osteoporosis, characterized by increased bone fragility, typically results from various factors such as aging, steroid use, or malabsorption. HO is a condition where bone forms abnormally in soft tissues. Risk factors that predispose to HO include male sex, spinal cord injury, trauma, surgery, and genetic factors. Treatment of HO is typically surgical resection and NSAIDs. Initial evidence supported the use of bisphosphonates for preventing ectopic bone formation post-trauma, but recent data failed to show significant benefit in HO prevention. This case presents a patient with unique challenges of both HO and bone fragility with multiple severe vertebral fractures. Case: A 44-year-old male patient had a major motor vehicle accident necessitating multiple recurrent abdominal surgeries. During one exploratory laparotomy, diffuse mesenteric calcifications were noted, indicative of HO. A baseline Dual X-ray Absorptiometry (DXA) scan revealed bone density of 1.003 g/cm2 and 0.788 g/cm2 at the spine and femoral neck, respectively, concerning for osteopenia. He was started on zoledronic acid in preparation for upcoming intestinal transplant. Few months after the transplant, he was started on daily tacrolimus and hydrocortisone for immunosuppression. Within months, he experienced sudden back pain while riding an elevator, and was found to have acute fractures in T8 and T9 vertebrae. A repeat DXA scan showed a further decline in bone density to 0.909 g/cm2 and 0.748 g/cm2 at the spine and femoral neck, respectively. Within a year, additional fractures occurred in the thoracic and lumbar spine (T10, T11, T12, L1, L2, L3, and L4), requiring multiple kyphoplasty interventions. Over time, worsening kyphosis, back pain, and height loss occurred, significantly affecting the patient's quality of life. He continued receiving yearly zoledronic acid infusions and underwent regular DXA scans, which revealed mild improvement in his bone density. Currently, there are no established guidelines specifying the optimal duration for bisphosphonate treatment in such cases. Therefore, our individualized treatment plan involves a tentative 10-year course of bisphosphonate treatment with yearly assessment of bone mineral density. Conclusion: Although the patient had some risk factors for osteoporosis, including daily steroid and tacrolimus use, the severity and frequency of his fractures suggested a potential synergy between osteoporosis and HO, where the formation of heterotopic calcifications may have been exacerbating his bone loss. The coexistence of osteoporosis and HO in this patient underscores the need for individualized care and establishment of treatment guidelines in patients with multiple bone disorders. Presentation: 6/3/2024

Application of Low-Temperature Ice Saline Bone Cement in Percutaneous Vertebroplasty

Percutaneous vertebroplasty uses the traditional method of bone cement filler to inject bone cement, which solidifies easily. We have established a new method to delay the solidification of bone cement (low-temperature ice saline bone cement) and compared the advantages of the new method and the traditional method of injecting bone cement. Eighty-two patients with osteoporotic vertebral compression fracture were divided into 2 groups by a retrospective study method: 40 patients in group A were treated with the traditional method and 42 patients in group B were treated with the new method. The leakage rate of bone cement, postoperative visual analog scale score, amount of bone cement in each vertebral body, operation time of bone cement, and number of bone cement fillers used were compared between the 2 groups. There was no significant difference in the bone cement leakage rate, postoperative visual analog scale score, the amount of bone cement in each vertebral body, and the number of bone cement fillers used between the 2 groups; the operation time of bone cement in the 2 groups was statistically significant, and the operation time in group B was significantly longer than that in group A. Low-temperature ice saline water bone cement has significant advantages in multiple vertebral fractures, a relatively large amount of bone cement injected into each vertebral body, and a long operation time, which is more suitable for beginners.

Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture.

To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF). A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis. CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023-0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97-43.22; p < 0.01). CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.

High bone fracture risk in a large modern cohort of liver transplant recipients.

Liver transplantation (LT) has historically been associated with a high prevalence of osteoporosis, but most of the available data date back to late 1990s-early 2000s with limited sample size. Our aim was to assess the prevalence of bone fragility fractures and contributing factors in a large modern cohort of liver transplant recipients. Retrospective study of 429 consecutive patients receiving liver transplantation from 1/1/2010 to 31/12/2015. Final cohort included 366 patients. Electronic radiological images (lateral views of spine X-rays or Scout CT abdominal scans) performed within 6months from LT, were blinded reviewed to screen for morphometric vertebral fractures. Symptomatic clinical fragility fractures were recorded from the medical records. Patients with fragility fractures in the cohort were 155/366 (42.3%), with no significant differences between sexes. Most sustained vertebral fractures (145/155, 93.5%), mild or moderate wedges, with severe fractures more frequently observed in women. Multiple vertebral fractures were common (41.3%). Fracture rates were similar across different etiologies of cirrhosis and independent of diabetes or glucocorticoids exposure. Kidney function was significantly worse in women with fractures. Independently of age, sex, alcohol use, eGFR, and etiology of liver disease, low BMI was significantly associated with an increased risk for fractures (adjusted OR 1.058, 95%CI 1.001-1.118, P = 0.046). Our study shows a considerable fracture burden in a large and modern cohort of liver transplant recipients. Given the very high prevalence of bone fractures, a metabolic bone disease screening should be implemented in patients awaiting liver transplantation.

Correlation study of multiple inflammatory indices and vertebral compression fracture: A cross-sectional study

BackgroundVertebral compression fractures (VCFs) are prevalent in patients with osteoporosis and pose significant health risks. Although chronic low-grade inflammation plays a crucial role in the pathogenesis of osteoporosis, the relationship between various inflammatory indices and the occurrence of fractures remains unclear. ObjectiveThis study aims to evaluate the correlation between multiple inflammatory indices, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI), and VCFs, to explore the significance of these indices in clinical application. MethodsClinical data of 310 patients diagnosed with osteoporosis from November 2020 to June 2023 in the hospital were collected. The general conditions between fracture and non-fracture groups were described. Spearman analysis and binary logistic regression analysis were used to assess the relationship between inflammatory indices and VCFs. Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of these inflammatory indices for VCFs. ResultsVCFs were diagnosed in 43.55 % of patients with osteoporosis. NLR(ρ = 0.169, P=0.003), MLR(ρ = 0.293, P<0.001), SII(ρ = 0.126, P=0.027), and SIRI(ρ = 0.273, P<0.001) were positively correlated with the occurrence of VCFs. NLR(OR=1.480, 95 %CI 1.114 ∼ 1.966, P=0.007), MLR(multiplied by 100, OR=1.048, 95 %CI 1.011 ∼ 1.087, P=0.011), and SIRI(OR=3.327, 95 %CI 1.510 ∼ 7.330, P=0.003) were independent risk factors for VCFs, hip bone mineral density (BMD) (OR=0.011, 95 %CI 0.001 ∼ 0.151, P=0.001) was an independent protective factor for VCFs. MLR(AUC 0.671, 95 % CI=0.610 ∼ 0.732, P <0.001) had relatively high clinical diagnostic efficacy. ConclusionThe neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI) are independent risk factors for vertebral compression fractures.

Progression of multiple vertebral fractures after denosumab discontinuation under treatment with romosozumab. A case-report

IntroductionDenosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon. Case presentationWe present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed. DiscussionOur clinical case illustrates the ineffectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option.

High prevalence of morphometric vertebral fractures opportunistically detected on thoracic radiograms in patients with non-functioning pituitary adenoma.

Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. We enrolled 156 patients (79M/77F, mean age 55.75 ± 12.94years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3.

Assessment of inter- and intraobserver agreement for META score in distinguishing osteoporotic from multiple myeloma vertebral fractures.

To conduct an independent assessment of inter- and intraobserver agreement for the META score as a tool for differentiating osteoporotic vertebral fractures and multiple myeloma vertebral fractures. This is a retrospective observational study. The magnetic resonance imaging analysis was made by two independent spinal surgeons. We designated a Subjective assessment, in which the surgeon should establish a diagnostic classification for each vertebral fracture based on personal experience: secondary to osteoporosis, categorized as a benign vertebral fracture (BVF), or attributed to multiple myeloma, categorized a malign vertebral fracture (MVF). After a 90-day interval, both surgeons repeated the evaluations. For the next step, the observers should establish a diagnosis between BVF and MVF according to the META score system, and both observers repeated the evaluations after a 90-day interval. The intra and interobserver reliability of the Subjective evaluation was studied using the kappa (κ) test. Then, the META evaluations were paralleled using the intraclass correlation coefficient (ICC). A total of 220 patients who had the potential to participate in the study were initially enrolled, but after applying the exclusion criteria, 44 patients were included. Thirty-three patients had BVF, and 12 patients presented MVF. Interobserver agreement for both Subjective evaluations moments (initial and 90-days interval) found a slight agreement for both moments (0.35 and 0.40 respectively). Kappa test for both META evaluations moments (initial and 90-days interval) found a moderate interobserver agreement for both moments (0.54 and 0.48 respectively). It was observed that the ICC calculated for the Initial evaluation using META score was 0.680 and that in the 90-days interval was 0.726, indicating regular to good agreement. Kappa test for intraobserver agreements for the Subjective evaluation presented moderate agreement for both Surgeons. On the other side, Kappa test for intraobserver agreements for the META evaluation presented substantial agreement for both Surgeons. The Intraclass Correlation Coefficient of the META score found presented an almost perfect agreement for both Surgeons. Intra and interobserver agreement for both surgeons were unsatisfactory. The lack of consistent reproducibility by the same observer discourages and disfavors the routine use of the META score in clinical decision making, when potentially cases of multiple myeloma may be present.

Abstract PO1-12-02: Impact of Discontinuation of Denosumab on Bone Health in Breast Cancer Patients

Abstract Denosumab (Dmab), an inhibitor of osteoclast activity and proliferation is approved for treatment of women on aromatase inhibitor (AI) therapy for early breast cancer (60 mg Q 6-months) and metastatic disease (120 mg Q 4-weeks) to protect against bone loss and prevention of skeletal-related events (SREs). 60 mg given twice a year has shown fracture reduction, especially in women on aromatase inhibitor therapy, and recent data supports benefits in disease free survival, bone-metastasis free-survival and overall survival with Dmab in early breast cancer. It appears superior in reduction of SREs versus zoledronic acid (ZA) in established skeletal metastatic disease; thus, a preferred choice in the oncology setting. In the osteoporosis setting, withdrawal of Dmab therapy leads to a “rebound” increase of bone resorption, rapid bone loss and potential vertebral fractures. Increased risk of spontaneous and multiple vertebral fractures has been seen in this patient population. To prevent this, after discontinuation of Dmab, the addition of another anti-resorptive such as ZA is initiated. Dmab withdrawal events are uncommonly reported in patients with metastatic skeletal disease due to generally poor prognosis. Dmab given as 120 mg/month in this setting may need to be curtailed for a variety of indications including hypocalcemia, major dental procedures, osteonecrosis of the jaw or atypical femoral fracture. In the oncologic setting, it is unclear if discontinuation of Dmab will lead to rebound bone resorption or increased incidence of fractures. We describe the case is of a 32-year-old woman with a history of T2N3M1, oligometastatic breast cancer (solitary bone metastases at L1, biopsy-proven) that was ER/PR/HER2 positive. She was treated with neoadjuvant trastuzumab, pertuzumab, taxotere and carboplatin followed by bilateral mastectomy, and radiation to chest wall and L1. She received total estrogen blockade initially with GnRH-agonist and exemestane and ultimately bilateral salpingo-oophorectomy plus exemestane. She continues pertuzumab and trastuzumab (80 treatments to date) for the past 5 years and denosumab 120 mg/month for 14 treatments and then every 3 months, 20 total treatments. Development of hip pain (regular runner) and concern for atypical fracture vs metastatic disease led to bone scan and PET/CT. Metastatic disease was ruled out and stress reaction was diagnosed. Dmab therapy was discontinued with monitoring of her metabolic bone turnover. 1 year after her last Dmab injection, bone turnover markers began to increase and ultimately demonstrated a very significant “rebound phenomenon.” Subsequently, a single dose of 120 mg denosumab decreased bone markers to previously low levels which remain low on routine monitoring, table below. In future, ZA will be initiated and continued on a yearly basis. Dmab has replaced ZA in managing bone health in breast cancer patients. Many oncologists use this without the assistance of bone health endocrinologists, who are an integral part of our cancer center. Bone modifying agents are often discontinued without consideration of the negative impact this may have. As this is a major survivorship issue, we document this case with literature review, to raise awareness for oncologists prescribing these medications. Citation Format: Susan Tannenbaum, Alvaro Alvarez Soto, Pamela Taxel. Impact of Discontinuation of Denosumab on Bone Health in Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-02.

Zoledronate After Denosumab Discontinuation: Is Repeated Administrations More Effective Than Single Infusion?

After denosumab (Dmab) discontinuation C-terminal telopeptide (CTX) levels increase, bone mineral density (BMD) decreases and multiple vertebral fractures (FX) may occur with relevant impacts on women's health. A sequential therapy with bisphosphonates is recommended, and the European Calcified Tissue Society (ECTS) proposed repeated zoledronate (ZOL) administrations in patients with persistently high CTX levels, although the efficacy of this schedule is unknown. In this retrospective study, we describe BMD changes and FX rate in 52 patients managed according to the ECTS recommendations. We measured CTX levels and administered ZOL after 1 month from Dmab withdrawal (t0). After 6 months (t1), we administered a second ZOL infusion, if CTX levels were ≥280 ng/L. BMD changes and FX rate were assessed on average after 17 months from Dmab withdrawal. Seventy-five percent of patients repeated ZOL infusion. In this group, spine BMD declined significantly (-5.5 ± 5.6%), while it remained stable in the group with CTX levels <280 ng/L (-0.1 ± 5.5%, P = 0.008). All fractured patients (9.6%) had received >5 Dmab injections and 2 ZOL infusions. The BMD worsening after Dmab withdrawal was associated with CTX t1 [odds ratio (OR) 2.9, interquartile range (IQR) 1.3-6.6, P = .009] and spine BMD gain during Dmab therapy corrected for the number of Dmab injections (OR 3.0, IQR 1.2-7.2, P = .014). A CTX level at t1 > 212 ng/L had 100% sensitivity in predicting the BMD loss. In patients with uncontrolled CTX levels after Dmab withdrawal, 2 ZOL infusions 6 months apart do not prevent BMD loss and FX.

On-time denosumab dosing recovered rapidly during the COVID-19 pandemic, yet remains suboptimal.

Timely administration of denosumab every 6mo is critical in osteoporosis treatment to avoid multiple vertebral fracture risk upon denosumab discontinuation or delay. This study aimed to estimate the immediate and prolonged impact of the COVID-19 pandemic on the timing of denosumab doses. We identified older adults (≥66yr) residing in the community who were due to receive denosumab between January 2016 and December 2020 using Ontario Drug Benefit data. We completed an interrupted time-series analysis to estimate the impact of the COVID-19 pandemic (March 2020) on the monthly proportion of on-time denosumab doses (183 +/-30d). Analyses were stratified by user type: patients due for their second dose (novice users), third or fourth dose (intermediate users), or≥5th dose (established users). In additional analyses, we considered patients living in nursing homes, switching to other osteoporosis drugs, and reported trends until February 2022. We studied 148 554 patients (90.9% female, mean [SD] age 79.6 [8.0] yr) receiving 648 221 denosumab doses. The average pre-pandemic proportion of on-time therapy was steady in the community, yet differed by user type: 64.9% novice users, 72.3% intermediate users, and 78.0% established users. We identified an immediate overall decline in the proportion of on-time doses across all user types at the start of the pandemic: -17.8% (95% CI, -19.6, -16.0). In nursing homes, the pre-pandemic proportion of on-time therapy was similar across user types (average 83.5%), with a small decline at the start of the pandemic: -3.2% (95% CI, -5.0, -1.2). On-time therapy returned to pre-pandemic levels by October 2020 and was not impacted by therapy switching. Although on-time dosing remains stable as of February 2022, approximately one-fourth of patients in the community do not receive denosumab on-time. In conclusion, although pandemic disruptions to denosumab dosing were temporary, levels of on-time therapy remain suboptimal.

Progression of vertebral deformity of prevalent vertebral fractures in the elderly: a population-based study

BackgroundLittle is known about the progression pattern of vertebral deformities in elderly patients with prevalent vertebral fractures. This population-based cohort study investigated the incidence, progression pattern, and risk factors of vertebral deformity in prevalent vertebral fractures over a finite period of four years in a population-based cohort study.MethodsA total of 224 inhabitants of a typical mountain village underwent medical examinations every second year from 1997 to 2009, and each participant was followed up for four years. The extent (mild, moderate, severe) and type (wedge, biconcave, crush) of prevalent vertebral fractures on spinal radiographs were evaluated using the Genant semi-quantitative method. Of these participants, 116 with prevalent vertebral fractures at baseline (32 men and 84 women; mean age: 70.0 years) were included in this study. The progression patterns of the 187 vertebral fractures with mild and moderate deformities (except severe deformity) were evaluated. Logistic regression analysis was used to identify the risk factors associated with deformity progression.ResultsThe progression of vertebral deformities was identified in 13.4% (25 vertebral fractures) of the total 187 prevalent (mild and moderate) vertebral fracture deformities over four years. Among the three deformity types, the prevalence of deformity progression was significantly lower in wedge-type vertebral fractures (P < 0.05). Age and number of prevalent vertebral fractures per participant were independent risk factors associated with the progression of prevalent vertebral deformities.ConclusionThis study clarified the natural history of the progression pattern of vertebral deformities in radiographic prevalent vertebral fractures in elderly individuals. Multiple vertebral fractures in the elderly present a risk for the progression of vertebral deformities.