Vertebral Fractures Research Articles

Percutaneous Mesh-Container-Plasty versus Percutaneous Kyphoplasty in the Treatment of Osteoporotic Compression Fractures with Up-Endplate Injury: A Retrospective Study

Percutaneous mesh-container-plasty(PMCP), a modified traditional percutaneous kyphoplasty(PKP)technique, is increasingly being used to treat osteoporotic vertebral compression fractures(OVCF) with up-endplate injury. This retrospective study aimed to compare the clinical and radiological results of PKP and PMCP for the treatment of this disease. We retrospectively analyzed the medical records of patients with osteoporotic compression fractures and upper endplate injuries treated at our hospital between January 2019 and December 2021. A total of 192 patients who met the inclusion and exclusion criteria were enrolled. Of these, 103 underwent PKP and 89 underwent PMCP. Key outcome measures included surgical safety, clinical efficacy, and radiological results. Both the PKP and PMCP groups showed significant improvements in VAS (Visual Analog Scale) and ODI (Oswestry Disability Index) scores postoperatively. Additionally, anterior vertebral body height ratio (AVBHr) and Cobb's angle improved in both groups, though no statistically significant difference was observed between them. The hospital stay duration was similar between the two cohorts. Notably, the PMCP group required a larger volume of bone cement injection, yet exhibited a significantly lower incidence of cement leakage and adjacent vertebral fractures (9/89 and 2/89, respectively) compared to the PKP group (24/103 and 11/103, respectively) (p < 0.05). Moreover, the PMCP group had shorter operation times (34.64 ± 9.88 minutes) and reduced fluoroscopy frequency (35.43 ± 5.46 instances) compared to the PKP group (27.23 ± 8.54 minutes and 23.87 ± 5.59 instances, respectively) (p < 0.05). PMCP provided superior clinical outcomes for the management of osteoporotic compression fractures with upper endplate injuries. It was associated with reduced operation and fluoroscopy times, as well as lower risks of adjacent vertebral fractures and cement leakage, compared to PKP.

7474 Demographic Patterns In Early Vertebral Fracture Diagnoses Among Women After Initiation Of Bisphosphonate Therapy

Abstract Disclosure: J.C. Lo: None. G.H. Tabada: None. M. Chandra: None. L.D. Carbone: None. T.C. Tan: None. J. Yang: None. E. Garcia: None. Introduction: Vertebral fractures (VFX) are a major osteoporotic fracture that identify women at high risk for subsequent fracture. However, less is known about demographic patterns in VFX diagnoses among women initiating osteoporosis therapy, including prior and subsequent VFX diagnoses. In this study, we examined racial and ethnic variation in VFX diagnoses among older women who initiated oral BP therapy in a large healthcare system. Methods: The study cohort included women aged 65-85y who initiated oral bisphosphonate (BP) therapy in 2008-2017, excluding those with selective bone disorders, metastatic cancer, multiple myeloma, kidney dialysis or transplant. Prior VFX diagnosis was based on ICD-9/10-CM diagnosis codes in the 5 years prior to or at BP initiation, excluding fracture codes related to open fracture or spinal cord injury. In the 2 years after BP initiation, new or initial encounter diagnoses of VFX were examined among those without prior VFX diagnoses. Findings were compared by race and ethnicity, overall and within age strata (65-74y, 75-85y). New VFX diagnoses after BP initiation were examined using Cox proportional hazard analyses, reporting hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 50,870 women aged 65-85y (56.5% age &amp;lt;75y) who initiated BP (66.9% White, 16.7% Asian/PI, 11.9% Hispanic, 3.2% Black), 2819 (5.5%) had prior VFX diagnosis. By race and ethnicity, 4.5% of White, 2.3% of Asian/PI, 3.5% of Hispanic, and 4.1% of Black women aged 65-74y had prior VFX diagnosis, increasing to 7.9% of White, 6.6% of Asian/PI, 7.9% of Hispanic, and 6.3% of Black women aged 75-85y. During 2 years follow-up after BP initiation and stratified by age, the incidence of new VFX diagnosis (per 1000 person-years) was 8.9 (7.9-9.9) for White, 3.2 (2.3-4.5) for Asian/PI, 7.1 (5.3-9.5) for Hispanic, and 6.8 (3.8-12.3) for Black women aged 65-74y, and 17.4 (15.9-19.0) for White, 13.0 (10.2-16.6) for Asian/PI, 14.2 (11.2-18.1) for Hispanic, and 6.1 (3.1-12.2) for Black women aged 75-85y. Adjusting for age, prior clinical fracture, and BP initiation year, the risk of new VFX diagnosis among women aged 65-74y (White as reference) was much lower for Asian/PI women (HR 0.40, CI 0.28-0.57) but not Black (HR 0.70, CI 0.38-1.29) and Hispanic (HR 0.80, CI 0.59-1.10) women. For older women aged 75-85y, the risk was much lower for Black women (0.36 (CI 0.18-0.72) but not Asian/PI (0.78, CI 0.60-1.02) and Hispanic (0.83, CI 0.64-1.07) women. Conclusion: Compared to White women, much lower VFX diagnosis among younger but not older Asian/PI women and among older but not younger Black women were seen in the 2 years after BP initiation. While new VFX diagnoses may represent prevalent or incident VFX and underlying fracture risk and continuation of BP may differ by group, these pilot findings support the need for more studies examining ethnic variation in VFX among older women, including differences by age. 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

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of &amp;gt;1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

7117 Cushings Conundrum: Taming The Hormone Hurricane

Abstract Disclosure: S. Syed: None. A. Poloju: None. A. Krueger: None. C. O'connor: None. Ectopic ACTH syndrome is a rare disease that presents with severe hypercortisolism that can be challenging to treat. This case reviews a patient with high- grade metastatic neuroendocrine tumor causing ectopic ACTH-related Cushing's syndrome and describes navigating these treatment challenges with an evidence-based and patient centered strategy to try to optimize care.Clinical case: This 32-year-old male, with a history of metastatic pancreatic neuroendocrine tumor and liver metastases, initially presented with dyspnea, hyperglycemia, and metabolic derangements. Agitated, with a systolic blood pressure of 190mm Hg, he exhibited notable hypokalemia (2.5mmol/L), hyperglycemia (508mg/dL), and elevated beta-hydroxybutyrate (3.60mmol/L). Random cortisol was 85.9ug/dL and ACTH 472pg/ml. Urgent cortisol control prompted etomidate infusion, lowering cortisol to 27ug/dL in 24 hours. Ketoconazole was initiated but discontinued later due to rising liver enzymes, Metyrapone and spironolactone were initiated and etomidate infusion titrated off. Hemorrhagic shock, DKA, and mental status changes complicated his course.Interventional radiology-guided hepatic artery embolization was performed. Post-procedure cortisol levels improved, metyrapone and spironolactone were stopped. Dexamethasone was initiated given concern for relative adrenal insufficiency during this time and was later switched to hydrocortisone, and eventually discontinued with normalizing cortisol levels. Octreotide and later lanreotide maintained stability for a year. He was readmitted with uncontrolled diabetes, hypertension, and vertebral compression fractures, requiring rapid control with etomidate infusion again. Metyrapone was reintroduced, facilitating etomidate tapering. Spironolactone was re-initiated. Bilateral adrenalectomy was discussed as definitive treatment for the ectopic ACTH syndrome (neuroendocrine cancer was deemed incurable, however he was considered elevated risk for surgery given other co-morbidities. Even with normalization of cortisol, he intermittently refused cares/medications. Conclusion: Managing ACTH-producing neuroendocrine tumors necessitates a multidisciplinary approach. In severe Cushing’s syndrome, etomidate infusion quickly normalizes cortisol but requires intensive care due to sedation risks. Ketoconazole and levoketoconazole carry a hepatotoxicity risk. Metyrapone and mitotane are alternatives but supply challenges exist. Osilodrostat, studied for short-term use, has limited data in ectopic ACTH syndromes. Bilateral adrenalectomy is an option if surgical risks are acceptable. Patient history influences therapeutic decisions, highlighting the need for a patient-centered approach. Presentation: 6/3/2024

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

Association between radius axial low-frequency ultrasound velocity and bone fragility in primary hyperparathyroidism.

Radius quantitative ultrasound measurement, that utilized a portable low-frequency (VLF) axial transmission ultrasound for assessing the properties of radius cortical bone in a non PHPT population revealed a possible role as a screening tool prior to DXA to evaluate fragility fracture. To evaluate this portable ultrasound device as a screening tool of skeletal fragility in PHPT patients. We enrolled 117 postmenopausal women with PHPT. Every subject had a DXA of femur, lumbar spine, non-dominant distal 1/3 radius, TBS measurement, VLF with a portable device and spine x- ray. The mean age of the patients was 68 ± 10 years. The measurement of agreement between radius DXA and VLF was: K = 0.43, p < 0.001. A lower radius US T-score, also adjusted for years since menopause and BMI, was associated with osteoporosis identified with DXA at lumbar and/or femoral neck sites: OR = 1.852 (CI 1.08, 3.18). All fractures were associated with femoral neck T-score: OR = 1.89 (95% CI 1.24, 2.89), as well as with total hip T-score: OR = 1.65 (95% CI 1.09, 2.50), and years since menopause: OR = 1.25 (95% CI 1.02, 1.54).Morphometric vertebral fractures were associated with years since menopause: OR = 1.28 (95% CI 1.02,1.61), femoral neck T-score OR = 1.96 (95% CI 1.227, 3.135), total hip T-score OR = 1.64 (95% CI 1.04, 2.60), TBS OR = 0.779 (95% CI 0.60-0.99), both ultra-distal radius T-score: OR = 1.50 (95% CI 1.05, 2.156), and radius US T-score: OR = 1.67 (95% CI 1.09, 2.56). VLF could be used for screening purposes prior to DXA to evaluate PHPT fracture risk, only in conditions in which DXA measurement cannot be performed.

7743 A Case Study of Ectopic Adrenocorticotropic Hormone Secretion from Pancreatic Neuroendocrine Tumor

Abstract Disclosure: K.S. Wei: None. J. Huang: None. Introduction: Pancreatic neuroendocrine tumors (PanNETs) are uncommon cancers that account for less than 2% of pancreatic malignancies. Even rarer are ACTH-producing NETs which may only become symptomatic until after metastasis. This case study examines the distinct presentation and diagnostic complexities associated with ectopic adrenocorticotropic hormone (ACTH) secretion from a PanNET. Clinical Case:A 42 year-old male with hypertension and type 2 diabetes initially presented to the hospital with increased abdominal girth for one month, bilateral lower extremity edema for two weeks, and generalized abdominal pain. He had unremarkable surgical, family, and social histories. Patient was afebrile, normotensive, saturating well on room air, with exam notable for a distended abdomen and 2+ bilateral pitting edema. Admission labs were notable for potassium of 2.4 (ref: 3.5-5.1 mmol/L). MRI abdomen showed hepatomegaly with numerous heterogeneously enhancing masses and an ill-defined pancreatic tail mass with involvement of the spleen. Liver biopsy showed well-differentiated neuroendocrine tumor, grade 2. He was started on octreotide 20mg q4weeks and capecitabine/temozolomide q4weeks. Two months later, the patient was readmitted after presenting with back pain for two days, found to have acute compression fractures of T9-L1 without spinal PET activity. At follow-up visit with endocrinology, he endorsed easy bruising and muscle weakness and had hypertension (161/96 mmHg) with hypokalemia. Random cortisol was 43.7 (ref: 2.5-11.9 mcg/dL). ACTH was 124 (ref: 6-50 pg/mL) despite receiving chemotherapy. 24-hour urine cortisol was 3,049 (ref: 4-50 mcg/24 hrs). He was diagnosed with ectopic Cushing’s disease from ACTH-producing PanNET leading to osteoporosis and fracture of the vertebral bodies. For the ectopic Cushing’s disease, he was started on ketoconazole 200mg BID with plan to start osilodrostat once approved. For the fracture, he is scheduled for Zometa infusion and IR kyphoplasty. Conclusion: This case offers several important clinical insights. In patients with PanNET with Cushingoid exam findings, ACTH-producing PanNET should be high on the differential. Most ACTH NETs are aggressive often with liver metastases, whereby metastatic disease will have already occurred by the time the Cushingoid features develop. The initial severe hypokalemia and hypertension should have prompted investigation for mineralocorticoid excess from hypercortisolism, which may have led to an earlier diagnosis of ectopic ACTH Cushing’s disease, thereby decreasing the possibility of developing vertebral fractures, uncontrolled diabetes and hypertension. Ketoconazole or osilodrostat may be used to treat Cushing’s disease from ACTH NETs. Presentation: 6/1/2024

7655 Genetic Mysteries Unveiled: Unusual Mutation Unraveled In Hypophosphatasia

Abstract Disclosure: A. Sharma: None. P. Katikaneni: None. S. Tanveer: None. K. Selk: None. Introduction: Hypophosphatasia (HPP), an inherited dental-osseous metabolic illness, is caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), which leads to a decrease in TNSALP enzymatic activity. Patients with HPP typically experience dental and skeletal mineralization issues as their most common symptoms; musculoskeletal abnormalities, numerous fractures, tiredness, and migraines are less common clinical presentations. Case Report: Our 75-year-old male patient initially presented 1.5 years prior following a spontaneous T12 vertebral fracture. A bone biopsy was performed and did not reveal evidence of malignancy. Testing for SPEP/UPEP was not consistent with myeloma, and thyroid testing was also unrevealing. His alkaline phosphatase level was consistently &amp;lt;40 IU/L since 1999. An evaluation was done for low alkaline phosphatase and secondary reasons for bone loss. This testing did not reveal vitamin D deficiency, parathyroid disease, hypophosphatemia, laboratory evidence of celiac disease, hypogonadism, or hypomagnesemia. A vitamin b6 level was markedly elevated at 119 ng/mL (ref range 2.1-21.7) while not on supplementation. He had noticed multiple fractures as a child, but he had written them off as minor injuries. He could clearly remember breaking his right wrist and clavicle. As an adult, he had rib fractures and a foot fracture. He was unable to recollect losing his primary teeth. Almost all his teeth are crowns or implants despite taking exceptional care of them. He did not have joint hypermobility. Genetic testing revealed the patient was heterozygous for an ALPL gene variant, c.876_882delinsT. It was a variant of undetermined significance at that time. His daughter also was found to have a low alkaline phosphatase and the same genetic test result. She also has experienced dental carries and joint pain. Our patient initiated teriparatide due to the need for more urgent therapy for extensive spinal surgery. He was later transitioned to asfotase alfa therapy and has not had any further fractures at the time of this report. Discussion: Hypophosphatasia is a rare inborn disorder due to mutations in the tissue nonspecific alkaline phosphatase gene ALPL and is characterized by low ALP levels. Affected individuals will also have elevated vitamin b6 levels and urinary phosphoethanolamine (PEA) levels. Early diagnosis of HPP is necessary to prevent bone fracture pain and improve quality of life. Inaccurate assessments can miss diagnoses of parents and other family members and even lead to lost opportunities to treat a patient with a substantial illness burden. This case highlights the mutation c.876_882delinsT as a likely pathologic variant in the ALPL gene. It also supports that patients with HPP can also respond to teriparatide treatment. Presentation: 6/2/2024

[Translated article] Management of spinal deformities caused by osteoporotic vertebral fractures

Osteoporosis and fragility play a significant role in the treatment and planning of patients with deformity secondary to osteoporotic vertebral fracture (OVF). The resulting deformity can present significant challenges for its management, both from a medical and surgical perspective. The need for a specific classification for these deformities, including the potential for the development of artificial intelligence and machine learning in predictive analysis, is emerging as a key point in the coming years. Relevant aspects in preoperative optimisation and management of these patients are addressed. A classification with therapeutic guidance for the management of spinal deformity secondary to OVF is developed, emphasising the importance of personalised treatment. Flexibility and sagittal balance are considered key aspects. On the other hand, we recommend, especially with these fragile patients, management with minimally invasive techniques to promote rapid recovery and reduce the number of complications.

7253 Changes In Bone Density Observed After Transitioning From Denosumab To Alendronate Or Zoledronic Acid

Abstract Disclosure: A. Khan: None. B.P. Ramchandani: None. R.A. Zielinski: None. J. Liu: None. F.S. Mirza: None. Introduction: Discontinuation of denosumab (Dmab) results in rebound increase in bone turnover and increased risk of vertebral fracture. Guidelines recommend that discontinuation of denosumab should be followed by an oral or intravenous bisphosphonate (BP), hormone therapy or selective estrogen receptor modulator (SERM). Hypothesis: We hypothesize that patients who received weekly alendronate (ALEN) after discontinuation of Dmab will have less of a decline in bone mineral density (BMD) compared to patients who received once yearly zoledronic acid (ZA). Methods: We conducted a retrospective chart review to compare the change in BMD and factors affecting BMD loss in patients who received sequential therapy with ZA versus ALEN. IRB approval was obtained. Patients were selected using Epic SlicerDicer if they had taken Dmab therapy from 2018 (year of epic implementation) onwards and had been transitioned to a BP. A total of 251 patients were initially selected. 35 patients met the inclusion criteria of being transitioned off to ALEN or ZA at least 1 year prior to date of data acquisition; 21 transitioned to ZA and 14 to ALEN. The rest of the patients were continuing Dmab and excluded from the analysis. BMD gain after Dmab therapy was evaluated. BMD change after 1 year of receiving sequential therapy was compared between the two groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Results: A total of 35 patients were included in data analysis with mean age of 73.7 + 9 years. The mean percentage gain in BMD achieved after Dmab therapy was 9.9 + 8.5%, 4.6 + 10.6%, and 6 + 5.2% at the LS, FN and TH respectively. The mean duration of Dmab therapy was 4.4 + 2.1 years. One year following sequential therapy, mean percentage BMD loss at the LS was 4.5% with ALEN and 3.0% with ZA (p-value: 0.59, 95% CI: -0.04 to 0.08). Following sequential therapy, mean percentage loss at FN was 2.2% with ALEN and 0.2% with ZA (p-value: 0.1895% CI: (-0.01 to 0.04), mean percentage loss at TH was 2.0 % with ALEN and 2.2% with ZA (p-value: 0.78, 95% CI: -0.03 to 0.02). Mean vitamin D level of all patients at time of starting sequential therapy was 45.9 + 12.9 ng/ml. Duration of prior bisphosphonate use before starting Dmab therapy did not have any significant effect on BMD loss after sequential therapy. All patients had vitamin D level in a good range at the beginning and end of the study period. Conclusion: There is invariably some decline in BMD when transitioning from Dmab to BPs. Although our data showed somewhat greater BMD loss at LS and FN with ALEN compared to ZA, this difference was not statistically significant and failed to reject the null hypothesis. These findings need to be evaluated further in larger prospective studies. Presentation: 6/3/2024

Age- and gender-dependent impact of titanium vertebral augmentation implants combined with cementing on subsequent vertebral fracture incidence: A comparative study with cementing alone.

To compare vertebroplasty (VP) and kyphoplasty (KP) with a titanium implantable vertebral augmentation device (TIVAD) in symptomatic subsequent vertebral compression fracture (SVCF) incidence among osteoporotic vertebral compression fracture (OVCF) patients stratified by age and sex. This retrospective cohort study involved OVCF patients aged ≥ 50, who underwent KP with TIVAD or VP in our hospital from 2014 to 2019. Subgroup analysis was conducted to evaluate the efficacy of KP with TIVAD and VP in patients stratified by age and sex. The study included 472 patients (VP group: 303; TIVAD group: 169). SVCF incidence rates were 15.2% for VP group and 14.8% for TIVAD group (P = 0.87). In subgroup analysis, TIVAD group showed significantly lower SVCF incidence than VP group in women aged 50-70 (2.1% vs 14.3%; P = 0.03) and had significantly higher SVCF incidence than VP group in women aged > 70 (24.2% vs 13.1%; P = 0.02). In men, adjacent SVCF incidence was significantly lower in TIVAD group than VP group (0% vs 14.1%; P = 0.03). Compared to VP, TIVAD is associated with lower symptomatic SVCF rate in men and younger women aged 50-70 but not in older women aged > 70. Age and gender may influence SVCF incidence. Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Vertebral body density role in determining vertebral osteoporotic fracture type and its progression.

Vertebral osteoporotic fractures (VOF) are among the most frequent fractures in the elderly, often leading to an impaired lifestyle and a high economic burden. Although a reduced bone mass density is considered one of the main risk factors for VOF, its role in determining the fracture type, using the AO spine-DGOU classification for osteoporotic thoracolumbar fractures, as well as its progression, is unknown. The current study aimed to: (1) reveal whether the bone density of the vertebral bodies of fractured and non-fractured vertebrae predicts the type of fracture, (2) examine whether bone density is associated with the initial and progressive collapse of the vertebral body, and (3) provide predictive measures for fracture progression. The study sample included 124 patients (40 males and 84 females) with an acute osteoporotic vertebral fracture who underwent a computerized tomography scan at the time of diagnosis and an x-ray at least 3 months later. The bone density of the fractured and adjacent (non-fractured) vertebrae was measured at diagnosis. The magnitude of the collapse and the progression of the fracture over time were calculated from height measurements of the vertebral bodies at diagnosis and follow-up. Age was a significant factor in predicting the fracture type and magnitude of collapse, whereas sex and bone density were not. The severity of the fracture was involved in predicting its progression, demonstrating that severe-type fractures tended to continue to collapse after diagnosis. However, when each type was examined independently, the density of the fractured vertebra had a protective effect on fracture progression. To conclude, identifying the type of fracture is beneficial in determining patient prognosis. Furthermore, the density of the fractured vertebra, the magnitude of collapse, and patient age are valuable predictors of fracture progression.

Screening for endogenous hypercortisolism in patients with osteoporosis and fractures: why, when and how.

Skeletal comorbidities are frequent and clinically relevant findings in Cushing's syndrome (CS) since an uncoupled suppressed bone formation and enhanced bone resorption leads to a marked skeletal damage with a rapid increase of fracture risk. Reduced Bone Mineral Density (BMD) has been consistently reported and osteopenia or osteoporosis are typical findings in patients with CS. Vertebral Fractures (VFs) are frequently reported and may occur even in patients with an only mild reduction of BMD. Since CS is diagnosed late due to often difficult biochemical and radiological confirmation as well as to signs and symptoms common in other much more frequent diseases an approach suggested for overcoming underdiagnosis is to screen patients with manifestations which may overlap with those of CS such as arterial hypertension, diabetes mellitus and osteoporosis. Our review will focus on the rationale and best practice for screening osteoporotic patients for CS.

Using an Ensemble of Segmentation Methods to Detect Vertebral Bodies on Radiographs.

Vertebral compression fractures may indicate osteoporosis but are underdiagnosed and underreported by radiologists. We have developed an ensemble of vertebral body (VB) segmentation models for lateral radiographs as a critical component of an automated, opportunistic screening tool. Our goal is to detect the approximate location of thoracic and lumbar VBs, including fractured vertebra, on lateral radiographs. The Osteoporotic Fractures in Men Study (MrOS) data set includes spine radiographs of 5994 men aged ≥65 years from 6 clinical centers. Two segmentation models, U-Net and Mask-RCNN (Region-based Convolutional Neural Network), were independently trained on the MrOS data set retrospectively, and an ensemble was created by combining them. Primary performance metrics for VB detection success included precision, recall, and F1 score for object detection on a held-out test set. Intersection over union (IoU) and Dice coefficient were also calculated as secondary metrics of performance for the test set. A separate external data set from a quaternary health care enterprise was acquired to test generalizability, comprising diagnostic clinical radiographs from men and women aged ≥65 years. The trained models achieved F1 score of U-Net = 83.42%, Mask-RCNN = 86.30%, and ensemble = 88.34% in detecting all VBs, and F1 score of U-Net = 87.88%, Mask-RCNN = 92.31%, and ensemble = 97.14% in detecting severely fractured vertebrae. The trained models achieved an average IoU per VB of 0.759 for U-Net and 0.709 for Mask-RCNN. The trained models achieved F1 score of U-Net = 81.11%, Mask-RCNN = 79.24%, and ensemble = 87.72% in detecting all VBs in the external data set. An ensemble model combining predictions from U-Net and Mask-RCNN resulted in the best performance in detecting VBs on lateral radiographs and generalized well to an external data set. This model could be a key component of a pipeline to detect fractures on all vertebrae in a radiograph in an automated, opportunistic screening tool under development.

Rationale and Protocol of the ETERNITY-ITA Study: Use of Etelcalcetide for Preserving Vitamin K-Dependent Protein Activity—An Italian Study

Background/Objectives: Chronic kidney disease and mineral bone disorders (CKD-MBD) are frequently associated with an increased risk of both vascular calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and bone Gla protein (BGP), have pivotal roles both for VCs and BFs. The VIKI study highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs beyond the beneficial effect of reducing PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age- and sex-matched patients treated with calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on an individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusions: This study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively.

Predictors of lumbar spine trabecular bone score in women with postsurgical hypoparathyroidism

Hypoparathyroidism is a rare disease that markedly reduces bone remodeling, leading to increased bone mineral density and changes in bone microarchitecture. However, it is currently unclear how these changes affect fracture risk. In this study, we investigated bone mass by dual-energy x-ray absorptiometry, the occurrence of morphometric vertebral fractures, and bone microarchitecture by assessing trabecular bone score in women with postsurgical hypoparathyroidism. We included 67 women with hypoparathyroidism aged 52.9 ± 12.3 years and 63 age (52.9 ± 12.3 years) and body mass index-matched controls, which were assessed for femoral and lumbar spine bone mineral density, trabecular bone score, and vertebral fractures by dual-energy x-ray absorptiometry. Women with hypoparathyroidism had significantly higher bone mineral density at the lumbar spine, femoral neck, and total hip compared with controls despite similar trabecular bone score values. Vertebral fracture assessment indicated that two women with hypothyroidism presented vertebral fractures, both aged over 65 years. Conversely, no vertebral fractures were detected in control women. In a multivariate linear regression model, we found that older age, diabetes, and lower lumbar spine mineral density were significant predictors of lower trabecular bone score values. Our findings indicate that vertebral fractures are not common among women with postsurgical hypoparathyroidism aged under 65 years. Moreover, trabecular bone score values were similar in women with hypoparathyroidism and age-matched controls and were associated with traditional risk factors for fractures, such as older age, type 2 diabetes, and lower spine bone mineral density. Lay summaryChronic parathyroid hormone deficiency decreases bone turnover and modifies skeletal properties, although the impact of these changes on fracture risk remains unclear. We studied 67 women with postsurgical hypoparathyroidism and 63 age and body mass index-matched healthy controls and found that bone mineral density is increased in women with hypoparathyroidism despite similar trabecular bone score values and a low occurrence of morphometric vertebral fractures. This suggests that the low bone turnover in hypoparathyroidism increases bone mass, but this is not accompanied by improved bone microarchitecture, indicating that trabecular bone score may be a valuable tool to complement the assessment of skeletal health and the risk of fractures in this condition.

Effects of Lumbar Spine Vertebral Fractures on Trabecular Bone Score (TBS): The Manitoba BMD Registry

Trabecular bone score (TBS) is a BMD-independent risk factor for fracture. During BMD reporting, it is standard practice to exclude lumbar vertebral levels affected by structural artifact. It is uncertain whether TBS is affected by lumbar spine fractures. The current study examined the effect of lumbar spine compression fractures on TBS measurements. We identified 656 individuals with vertebral fractures (mean age 75.8 ± 7.9 years, 90.9% female) who had lumbar spine DXA, TBS measurements from L1-L4 and vertebral fracture assessment (VFA) for identifying vertebral fractures. There were 272 cases with lumbar spine fractures and 384 controls with only thoracic spine fractures. L1 TBS and BMD were significantly greater in those with than without lumbar fractures (p< 0.001) but did not significantly differ for other vertebral levels or for L1-L4 combined. TBS and BMD measurements were then renormalized to remove level-specific differences (denoted rTBS and rBMD). The mean difference (all fractured minus all non-fractured vertebrae) was +0.040 (+3.3%) for rTBS and +0.088 g/cm2 (+9.5%) for rBMD (both p <0.001). The largest effect was for L1 with mean difference +0.058 (+4.9%) for rTBS and +0.098 g/cm2 (+10.6%) for rBMD (both p <0.001). The mean difference between fractured and non-fractured levels for rTBS was +0.028 (+2.4%) for grade 1, +0.036 (+3.0%) for grade 2 and +0.059 (+5.0%) for grade 3 fractures; for rBMD +0.051 (+5.5%), +0.076 (+8.2%) and +0.151 (+16.4%) g/cm2, respectively. The impact of excluding lumbar vertebral levels with fracture from the L1-L4 TBS measurement overall was small (-0.011 [-1.0%]; p<0.001) and was also small for grade 3 fractures (-0.020 [-1.7%]; p<0.001). In summary, TBS is mildly increased by VFA-confirmed lumbar vertebral fractures, but the percentage effect is much smaller (less than half) than seen for BMD and minimally affects TBS measured from L1-L4. This would support the use of L1-L4 without exclusions in individuals with lumbar vertebral fractures.

Association of oral hypofunction with aspiration pneumonia, fractures, and mortality in older Japanese adults.

In Japan's public health system, dentists can assess and intervene in oral hypofunction cases. However, the associations between oral hypofunction and health outcomes and costs remain unclear. This study aimed to identify these associations. This retrospective cohort study using a Japanese health insurance claims database included 45 916 individuals aged ≥65 years who underwent dental examinations for oral hypofunction. The primary outcomes were incidence rates of aspiration pneumonia, femoral or vertebral fractures and all-cause mortality. Secondary outcomes were annual medical and dental costs. We used competing risk regression and Cox models to estimate primary outcomes, and gamma regression models for secondary outcomes. The adjusted hazard ratios were 0.84 (95% CI 0.74-0.96) for the incidence of aspiration pneumonia, 1.11 (1.02-1.21) for the incidence of femoral or vertebral fractures and 1.27 (1.07-1.50) for all-cause mortality in individuals with oral hypofunction compared with those without. The adjusted relative risk was 1.05 (1.01-1.10) for annual medical costs and 0.94 (0.81-1.09) for annual dental costs in individuals with oral hypofunction compared with those without. Individuals with oral hypofunction were at increased risk of femoral or vertebral fractures and all-cause mortality, and they incurred significantly higher annual medical costs, compared with those without this condition. Notably, they showed a lower risk of aspiration pneumonia, suggesting potential benefits of dental intervention. Integrating dental care into medical strategies might be necessary to improve health outcomes and reduce healthcare costs for those with oral hypofunction. Geriatr Gerontol Int 2024; 24: 1053-1059.

Radiographic Diagnosis of Osteoporotic Vertebral Fracture in Older Women and Men Based on Statistical Probability.

A radiographic gold standard to distinguish osteoporotic vertebral fractures (VFs) from nonosteoporotic VFs does not exist. Radiographic fracture-shaped vertebral deformity (FSVD) is common among young populations with normal bone strength. FSVD in an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely associated with compromised bone strength. For more severe grade deformities or when a vertebra is collapsed, experienced readers can make an osteoporotic VF diagnosis with a high degree of certainty. In milder cases, radiographic osteoporotic VF is often diagnosed based on a high probability rather than an absolute diagnosis. For older women, three nonadjacent minimal grade OLVFs (< 20% height loss), one minimal grade OLVF and one mild OLVF (≥ 20∼25% height loss), or one OLVF with ≥ 25% height loss meets the diagnosis of osteoporosis. For older men, a single OLVF with ≥ 33 to 40% height loss is insufficient to suggest the patient has osteoporosis.