Wermers, Robert A.

Biparietal osteodystrophy, also known as bilateral parietal calvarium bone thinning, is a rare calvarial condition characterized by loss of diploic bone within the parietal region. Although historically described in anthropologic and radiologic literature, current understanding of its epidemiology, pathogenesis, clinical relevance, and management remains fragmented. This review synthesizes current evidence and highlights emerging studies on biparietal osteodystrophy. Epidemiologic reports indicate that biparietal osteodystrophy affects a broad age range but appears most frequently in older adults, with several series suggesting a slight female predominance. Prevalence is difficult to estimate due to incidental detection, though modern imaging has increased recognition of the condition. Histologically and anatomically, biparietal osteodystrophy is marked by thinning of the outer table and loss of the diploic space, with little osteoblastic or osteoclastic remodeling. Proposed pathogenic mechanisms include chronic degenerative change, impaired vascular supply to the diploë, and other theories, although no single explanation fully accounts for its complete presentation. Clinically, most patients remain asymptomatic, with complications such as calvarial fractures and traumatic brain injury being rare but highlighting the structural vulnerability associated with severe thinning. Management strategies are not standardized, and the use of anti-osteoporotic drugs and cranioplasty has been reported to offer benefit in select cases, although no treatment has been formally validated for biparietal osteodystrophy. As the understanding of biparietal osteodystrophy continues to evolve, future research is needed to clarify its natural history, identify potential etiologic pathways, and establish evidence-based management guidelines.

Abstract Context Osteoanabolic therapy for osteoporosis should be followed by antiresorptive treatment (“consolidation”) to preserve bone mass. Although osteoanabolic therapy is increasingly endorsed for primary fracture prevention, real-world implementation of consolidation remains unknown. Objective To assess patterns and predictors of timely consolidation after osteoanabolic therapy for primary fracture prevention. Methods We conducted a retrospective cohort study using US commercial, Medicare Advantage, and traditional Medicare claims data. Adults aged ≥50 years who initiated romosozumab, teriparatide, or abaloparatide between 2011 and 2022 were included. The primary outcome was timely consolidation, defined as initiation of an antiresorptive medication within 3 months after osteoanabolic therapy. Secondary outcomes included delayed consolidation (initiation >3 months after completion), osteoanabolic restart following a treatment gap, and no consolidation therapy. We further distinguished participants who completed the full osteoanabolic course, defined as ≥12 months for romosozumab and ≥18 months for teriparatide or abaloparatide. Multivariable logistic regression models were used to identify predictors of consolidation patterns. Results Among 15 389 patients (mean age 70.6 years; 89% women; 85% White), 30% completed osteoanabolic therapy (median, 12.9 months for romosozumab; 23.4 months for teriparatide/abaloparatide). Overall, 25% had timely consolidation, 24% delayed consolidation, 12% restarted osteoanabolics, and 40% had no consolidation; only 12% completed therapy with timely consolidation. Timely consolidation was more likely with endocrinology (OR 1.31; 95% CI, 1.17-1.48) or rheumatology (OR 1.45; 1.30-1.62) vs primary care, and less likely among patients aged 50-64 years (OR 0.67; 0.58-0.77) vs 65-74, those enrolled in Medicare Advantage (OR 0.85; 0.74-0.98) vs traditional Medicare, or those recently hospitalized (OR 0.88; 0.80-0.97). Odds increased over time (OR 4.27; 3.63-5.05 for 2021 vs 2011 starts). Conclusion Only 1 in 4 patients received timely consolidation therapy after osteoanabolic treatment, and 1 in 8 completed the full sequence. Strategies to improve consolidation in primary fracture prevention are needed.

Introduction Previous studies have demonstrated that C 11 choline positron emission tomography/computed tomography (Choline-PET/CT) can localize abnormal parathyroid glands in the reoperative setting. This study assesses a large volume of patients with primary hyperparathyroidism (1HPT) who underwent Choline-PET/CT to confirm its utility in the setting of negative or equivocal conventional imaging. Methods All patients who underwent Choline-PET/CT for evaluation of 1HPT from July 2017 to July 2024 at a single institution were reviewed. Inclusion criteria were patients who underwent parathyroidectomy and had lab testing to assess for cure (defined as >50% drop from baseline PTH and into normal range, or resolution of hypercalcemia at follow-up). Sensitivity, positive predictive value (PPV), false negative rate (FNR), and accuracy were compared to conventional imaging (neck ultrasound, parathyroid scan, and parathyroid four-dimensional CT (4D-CT)). Subgroup analysis was conducted comparing sensitivity of modalities among index operations and separately in reoperations. Results 84 patients were included for analysis. 61 failed to localize on at least one conventional modality, and 15 failed to localize on all conventional studies. 67 patients (80%) achieved cure, of which 53 were reoperations. Choline-PET/CT outperformed conventional modalities across sensitivity, PPV, FNR, and accuracy. Choline-PET/CT also outperformed conventional modalities when comparing sensitivity in both subgroups. Conclusion C 11 choline-PET/CT is a valuable imaging modality in the reoperative setting and demonstrates utility for index operations. It provides localization when other modalities fail and allows for a high surgical cure rate. Further investigation into its utility as a primary imaging modality is warranted.

Abstract Disclosure: J.R. Hewlett: None. J.G. Sfeir: None. R.A. Wermers: None. J.J. Schmitz: None. Percutaneous ethanol ablation (PEA) is a non-surgical technique used in the management of hyperparathyroidism (HPT) since the 1980s. Previously published cohorts are small and/or focused on patients with primary hyperparathyroidism (PHPT) in the setting of multiple endocrine neoplasia type 1 (MEN1). New randomized controlled trial data suggests similar response rates between parathyroidectomy and PEA (98.5% vs 91.1%) for uniglandular disease, and a previously published cohort of PEA in patients with MEN1 and recurrent multiglandular PHPT at our institution reported post-PEA normocalcemia in 74.5% of patients. This retrospective cohort study examined the treatment response to PEA in those with PHPT (including MEN1) and tertiary HPT (THPT) at a single institution between 1997-2023. Those with secondary hyperparathyroidism or eucalcemic PHPT were excluded. The primary outcome was a serum calcium ≤10.1 mg/dL at 3-6 months and secondary outcomes included number and volume of ethanol injections, time to recurrence of HPT, and complications of PEA. A total of 83 patients were included. Most were women (62.7%) and the median age at diagnosis of HPT was 40 years. The majority had PHPT (90.4%), and many (86.7%) had previously undergone surgery. The most common indications for PEA were risk for hypoparathyroidism with additional surgery (72.3%) poor surgical candidacy (16.9%), and patient preference (8.4%). The mean calcium was 10.7 mg/dL (95% CI 10.56-10.85) and the mean PTH was 164 pg/mL (95% CI 120.6-208.3) prior to PEA. The mean number of ethanol injections was 3.0 (95% CI 2.6 – 3.4) and the cumulative volume of ethanol was 1.2 mL (95% CI 1.0-1.4). At 3-6 months, 68.3% of treated patients had calcium ≤10.1 mg/dL with a mean value of 9.4 mg/dL (95% CI 9.1-9.6). Of those, 42% did not have recurrence at most recent follow-up. Of those with recurrence, a post-PEA calcium ≤10.1 mg/dL at 3-6 months was associated with a longer time to recurrence than those without (36.9 months versus 3.75 months; P=0.0009). There was no significant difference between the number of times (P=0.56) or the volume (P=0.41) of ethanol injected between those with calcium of ≤10.1 mg/dL at 3-6 months and those without. Hypocalcemia was observed in 8 (9.6%; transient in 75%), hypoparathyroidism in 3 (3.6%; transient in 66.7%), laryngeal nerve injury in 2 (2.4%; transient in 50%), and hoarseness in 9 (10.8%; transient in 100%) patients. This is the largest North American cohort of patients who received PEA for HPT and represents a broader review of HPT than previously published. Our rate of post-PEA eucalcemia is lower than previously reported, however this cohort was complex with a high proportion of multiglandular disease (80.7%), MEN1 (39.8%) and prior surgeries (mean 1.7 per person; 95% CI 1.5-1.9). PEA remains a safe and effective treatment for patients with recurrent HPT, especially those at high risk of post-surgical hypoparathyroidism. Presentation: Monday, July 14, 2025

Abstract Disclosure: P. Hopmann: None. S. Lund: None. T. Foster: None. B. Dy: None. T. McKenzie: None. G. Johnson: None. R.A. Wermers: None. M. Lyden: None. Background: Previous studies have demonstrated that C11 choline positron emission tomography/computed tomography (Choline-PET/CT) can localize abnormal parathyroid glands in the re-operative setting. This study assesses a large volume of patients with primary hyperparathyroidism (1HPT) who underwent Choline-PET/CT to confirm its utility in the setting of negative or equivocal conventional imaging. Methods: All patients who underwent Choline-PET/CT for evaluation of 1HPT from July 2017 to July 2024 at a single institution were reviewed. Inclusion criteria were patients who underwent parathyroidectomy and had lab testing to assess for cure (defined as >50% drop from baseline PTH and into normal range, or resolution of hypercalcemia at follow-up). Sensitivity, positive predictive value (PPV), false negative rate (FNR), and accuracy were compared to conventional imaging (neck ultrasound, parathyroid scan, and parathyroid four-dimensional CT (4D-CT)). Subgroup analysis was conducted comparing sensitivity of modalities among index operations, and separately in re-operations. Results: 176 patients were identified. 85 underwent parathyroidectomy, 1 patient was excluded due to lacking data to evaluate for cure. Of 91 patients who did not undergo parathyroidectomy, 45 were non-localizing on all imaging, and 46 had positive Choline-PET/CT findings but opted against surgery due to mild disease or prohibitive re-operative risk. Of the included 84 parathyroidectomy patients, 61 failed to localize on at least one conventional modality, and 15 failed to localize on all conventional studies. 67 patients (80%) achieved cure, of whom 53 were re-operations (range of 1-4 prior operations, average 1.5). Choline-PET/CT outperformed conventional modalities across sensitivity, PPV, FNR, and accuracy. Among index operations, Choline-PET/CT had significantly higher sensitivity than conventional modalities (100% vs 27% for ultrasound, 30% for parathyroid scan, 29% for 4D-CT; p values ≤0.01). This was also true in re-operations (95% for Choline-PET/CT vs 13% for ultrasound, 30% for parathyroid scan, 32% for 4D-CT; p values <0.01). Conclusion: C11 choline-PET/CT is a valuable imaging modality in the re-operative setting and demonstrates utility for index operations. It provides localization when other modalities fail and allows for a high surgical cure rate. Further investigation into its utility as a primary imaging modality is warranted. Presentation: Monday, July 14, 2025

Abstract Background Percutaneous ablation of parathyroid adenomas provides a minimally invasive treatment option for primary hyperparathyroidism. However, the overall performance of this technique remains underexplored. This meta-analysis evaluates the effectiveness and safety of various ablation techniques for parathyroid adenomas. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, multiple databases, including Ovid MEDLINE and Cochrane, were systematically searched. Studies that provided separate data for radiofrequency (RF), microwave ablation (MWA), and ethanol ablation technique were included. Outcomes of interest were changes in serum calcium, PTH, and phosphorus levels, along with normocalcemia rates at 6 to 12 months after ablation. Safety outcomes included transient hoarseness, permanent hoarseness, severe hemorrhage, major complications, and severe hypocalcemia. Data were pooled using a random-effects model, with pooled prevalence and 95% CIs calculated. Also, the publication bias was assessed with Egger's test for each outcome measure. Results Twenty studies (815 patients) were included. The posttreatment normocalcemia rate at 6 to 12 months was 85.6% (95% CI, 80.48-90.72). Serum PTH and calcium levels significantly decreased, with mean differences of 101.49 pg/mL (95% CI, 73.50-129.48) and 0.39 mmol/L (95% CI, 0.34-.45), respectively. Permanent hoarseness and major complications were rare, with incidences of 0.28% (95% CI, 0.00-1.05) and 0.31% (95% CI, 0.00-1.09). The safety and efficacy outcomes of RF, MWA, and ethanol ablation were comparable. Conclusion Our findings indicate that percutaneous ablation of parathyroid adenomas is safe and effective within the first year of the treatment. Additionally, they suggest that RF, MWA, and ethanol ablation techniques can each be employed depending on patients' needs without particular limitations.

Abstract Disclosure: K. Gunter: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. R.A. Wermers: Research Investigator; Self; Inozyme Pharma. R. Fuhr: Employee; Self; Parexel GmbH. Research Investigator; Self; Inozyme Pharma. D. Schnabel: Research Investigator; Self; Inozyme Pharma. A. Besancon: Research Investigator; Self; Inozyme Pharma. M.A. Nour: Research Investigator; Self; Inozyme Pharma. D. Wenkert: Stock Owner; Self; Inozyme Pharma. Y. Sabbagh: Employee; Self; Inozyme Pharma. Stock Owner; Self; Inozyme Pharma. Background: ENPP1 Deficiency is a rare disorder due to inactivating mutations in the ENPP1 gene that result in low levels of inorganic pyrophosphate (PPi), a critical regulator of mineralization. Subsequent pathologic soft tissue calcification results in severe vascular calcification and ∼50% infant mortality. By early adolescence the majority of survivors develop FGF-23 mediated hypophosphatemic rickets, characterized by bone deformities, short stature, joint/ligament calcification and musculoskeletal pain. No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product. Purpose: To describe the safety, tolerability, immunogenicity, and exploratory efficacy (bone and mineral metabolism biomarkers and clinical outcomes) of INZ-701 in adults with ENPP1 Deficiency through the end of the phase 2 study period (week 48). Methods: Phase 1/2, multicenter, open-label, multiple ascending dose study including three adults in each of three dose cohorts (0.2, 0.6 and 1.8 mg/kg, total N=9) with genetic variants in ENPP1 and PPi <1300 nM (NCT04686175). Participants were dosed subcutaneously on Day 1, then twice weekly from Day 8 to end of study. Data through wk 48 as of July 6, 2023 are included; topline wk 48 data will be presented. Per protocol, participants may continue to receive INZ-701 beyond wk 48. Results: Rapid increase in mean PPi from baseline of 426±407 nM was noted in all patients, reaching the healthy volunteer range within 6 hrs of the first dose with sustained elevation through wk 48. Mean PPi across the 0.2, 0.6 and 1.8 mg/kg dose cohorts from day 32 to wk 48 was 1299±131 nM, 1356±136 nM, and 1282±81 nM, respectively. There were improvements from baseline to wk 48 in mean pooled FGF-23 (-22 pg/mL) and serum phosphate (+0.18 mg/dL), with dose-dependent changes in bone specific alkaline phosphatase consistent with bone healing. DEXA revealed improvements in spine BMD and BMC. There were trends towards improvement in mean % predicted change in 6MWT from baseline to wk 48: cohort 1, 76.7% (SE 10.5) to 85.0% (SE 3.0); cohort 2, 52.2% (SE 10.9 ) to 79.0% (SE 2.9); cohort 3, wk 48 data not available. Improvements were also observed in physician and patient global impression of change score (with no patients deteriorating) and PROMIS pain intensity score. INZ-701 was well tolerated with no drug-related serious or severe (> grade 2) adverse events. Low titers of non-neutralizing anti-drug antibodies (≤160) were observed in 7/9 patients. Long half-life of approximately 126 hours suggests the potential for once-weekly dosing. Conclusions: In adults with ENPP1 Deficiency, INZ-701 was well tolerated with no related serious or severe adverse events. INZ-701 demonstrated a rapid and sustained increase in PPi levels from baseline to week 48 with corresponding improvements in bone mineral biomarkers, functional performance, and patient and physician-reported outcomes. Presentation: 6/3/2024

Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.

Abstract Elevated 1,25-dihydroxyvitamin D (1,25(OH)2D) is a rare cause of non–parathyroid hormone (PTH)–mediated hypercalcemia seen in granulomatous disease, malignancy (most often lymphoma), or genetic mutations. Therapeutic options are limited. We report the case of a 67-year-old White man with nonmalignant, nongranulomatous, 1,25(OH)2D-mediated hypercalcemia treated successfully with cinacalcet. At presentation, he had hypercalcemia, hypercalciuria with recurrent nephrolithiasis, low PTH, elevated 1,25(OH)2D, and normal 25-hydroxyvitamin D. The 1,25(OH)2D levels were inappropriate in the setting of hypercalcemia with low PTH. Evaluations for sarcoidosis, tuberculosis, and malignancy were negative. Genetic testing showed biallelic variants in the CYP24A1 gene. Cinacalcet was trialed and showed normalization of calcium levels. On cinacalcet, biochemical indices showed a slight increase in 1,25(OH)2D and 24-hour urine calcium and mild decrease in PTH. He briefly experienced symptomatic hypocalcemia that resolved after reducing cinacalcet dose. Due to limited symptomatic benefit, he opted to stop cinacalcet. Additional follow-up showed intermittently elevated serum calcium levels after stopping cinacalcet, most recently 10.3 mg/dL. Cinacalcet may be a therapeutic option in nonmalignant, 1,25(OH)2D-mediated hypercalcemia. Further study is necessary to confirm efficacy, understand risks and benefits, and elucidate mechanism(s) of action.