JBMR Plus最新文献

{"title":"Synergistic effects of diabetic neuropathy and kidney function decline on second metatarsal skeletal health and foot function: a pilot study.","authors":"Victor A Cheuy, Saghi Sadoughi, Hasung Moon, Jalen Ellis, Rodney Gross, David R Sinacore, Mary K Hastings, Richard B Souza, Galateia J Kazakia","doi":"10.1093/jbmrpl/ziag058","DOIUrl":"10.1093/jbmrpl/ziag058","url":null,"abstract":"<p><p>A discouraging increase in diabetes-related nontraumatic lower-extremity amputations (NLEA) has occurred over the last decade. Individuals with diabetic neuropathy (DMPN) and CKD are at the highest risk for NLEA. Despite the critical implications, little is known about the factors that initiate the cascade of events leading to NLEA, limiting early and effective interventions. We aimed to develop and implement a technique for quantifying metatarsal bone density and microstructure using HR-pQCT. Twelve participants were enrolled: <i>n</i> = 3 healthy controls (CON; 57±4 yr, BMI 30±13 kg/m², eGFR 106±4 mL/min/1.73 m²), <i>n</i> = 3 who had type 2 diabetic neuropathy with estimated glomerular filtration rate (eGFR) stage 1 (DMPN; 66±2 yr, BMI 27±3 kg/m², eGFR 96±2 mL/min/1.73 m²), and <i>n</i> = 6 who had type 2 diabetic neuropathy with eGFR defined stages 2-4 (DMPN+eGFR_2-4; 69±10 yr, BMI 28±3 kg/m², eGFR 64±20 mL/min/1.73 m²). Participants underwent assessments including HR-pQCT of the second metatarsal, dynamic plantar pressure measurements, and multi-segment foot biomechanics analysis during gait. Between-group and pooled correlational analyses were performed. The DMPN+eGFR_2-4 group exhibited the highest cortical porosity at the mid-diaphysis, the highest pressure-time integrals at the hindfoot and for the total foot, the lowest intersegmental foot excursions, and lowest maximum ankle power. Correlation analyses revealed strong relationships between eGFR and cortical porosity (<i>r</i>=-0.868, <i>p</i><.001), stance hindfoot excursion (<i>r</i>=0.662, <i>p</i>=.027), swing toe excursion (<i>r</i>=0.759, <i>p</i>=.007), swing forefoot excursion (<i>r</i>=0.823, <i>p</i>=.002), swing hindfoot excursion (<i>r</i>=0.745, <i>p</i>=.007), and ankle power (<i>r</i>=0.717, <i>p</i>=.013). Skeletal deterioration, abnormal loading, and poor biomechanics underscore the compounded effects of DMPN and eGFR decline on foot health, likely a consequence of CKD-mineral bone disorder syndrome. These findings suggest potential targets for intervention to prevent NLEAs in this high-risk population. Further research is needed to explore the interaction between DMPN and CKD and targeted therapeutic strategies to improve clinical outcomes.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag058"},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for atypical femur fractures with and without bisphosphonate treatment: a national nested case-control study.","authors":"Rasmus Mikiver, Rickard Sand, Hans Peter Bögl, Georg Zdolsek, Daphne Wezenberg, Karl Michäelsson, Johan Lyth, Jörg Schilcher","doi":"10.1093/jbmrpl/ziag059","DOIUrl":"10.1093/jbmrpl/ziag059","url":null,"abstract":"<p><p>Atypical femur fractures (AFF) are rare stress fractures linked to long-term bisphosphonate (BP) use. However, since some patients develop AFF without BP exposure (BP-naïve), additional mechanisms have been proposed. In this study, we tested medication use, clinical characteristics, and femoral geometry. We started with a hypothesis that BP-naïve patients would have additional risk factors in these areas compared with BP-users. We included 172 patients aged ≥55 yr who sustained AFF in Sweden between 2008 and 2010. Among them, 134 had used BPs prior to the fracture and 38 had not. All fractures met the 2014 ASBMR major criteria for AFF. Data on medication use, comorbidities, and demographics were extracted from national registers, and radiographs were reviewed to assess femoral geometry. All statistical models were adjusted for sex and age. We found that among BP-naïve patients, male sex was more common (21.1%) than among BP-users (3.0%). Additionally, BP-naïve patients were less likely to use calcium supplementation (23.7% vs 90.3%, OR 0.04, 95% CI 0.01-0.10), corticosteroids (13.2% vs 35.8%, OR 0.18, 95% CI 0.05-0.52), proton pump inhibitors (23.7% vs 41.8%, OR 0.36, 95% CI 0.14-0.85), and beta-blockers (28.9% vs 47.0%, OR 0.43, 95% CI 0.18-0.97). Moreover, BP-naïve patients had fewer diagnosed bone disorders, including osteoporosis (5.3% vs 34.3%, OR 0.10, 95% CI 0.02-0.38). Bisphosphonate-naïve patients did have a higher lateral-to-medial cortical thickness ratio (1.00 vs 0.90, <i>p</i> < .01); however, other geometric differences were minor and did not support the hypothesis. The absence of identifiable mechanisms for stress fracture formation suggests that future research should test factors not captured in registry data or femoral geometry. Possibly, physical activity levels or subtle bone metabolic conditions may be contributing to the pathogenesis of AFF, particularly in BP-naïve individuals.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag059"},"PeriodicalIF":3.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional visualization of nerves in bones of the human hand in osteoarthritis.","authors":"John-Paul Fuller-Jackson, Richard Tee, Jenny Thai, Eugene T Ek, Stephen Tham, Jason Ivanusic","doi":"10.1093/jbmrpl/ziag055","DOIUrl":"10.1093/jbmrpl/ziag055","url":null,"abstract":"<p><p>Bone is innervated by nerves that have important roles in signaling bone pain, regulating bone homeostasis and remodeling, control of bone vasculature and hematopoiesis. However, a detailed knowledge of how nerves influence bone function is lacking, which has contributed to significant challenges for clinicians in successfully managing bone disease. In this study, we used tissue clearing and light-sheet microscopy to visualize and explore the 3D distribution of nerves in human bone with a view to better understand how nerves are distributed throughout different parts of the small bones of the hand. Human hand bones were obtained from patients undergoing excision due to advanced osteoarthritis. Bones were fixed and cleared using an optimized solvent-based clearing protocol. Nerves in the bone were immunolabeled using an antibody directed against a pan-neuronal marker (protein gene product 9.5). Samples were imaged using light-sheet microscopy (Ultramicroscope Blaze, Miltenyi Biotec). Three-dimensional visualization and analyses were performed with Imaris (Bitplane). There is extensive innervation of the small bones of the human hand. Immunolabeled nerves followed blood vessels into each bone via nutrient foramina and branched extensively within trabecular bone and marrow cavity spaces. Many axons had a typical corkscrew morphology associated with the innervation of the vasculature, and many terminated as free nerve endings, including in osteochondral channels beneath articular surfaces. Nerve entry points and their distribution through each of the different bones varied. There was evidence of a greater density of innervation in areas where cartilage had degenerated, relative to those where cartilage was intact. This is the first detailed 3D visualization of the neuroanatomical distribution of nerves in intact human bone. This approach to visualizing nerves in bone will be useful in informing the rational design of approaches to the management of a variety of skeletal pathologies, including pain management for osteoarthritis of the hand joints.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag055"},"PeriodicalIF":3.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of mechanical unloading on the irisin precursor, FNDC5, in skeletal muscle of sheep as a large animal experimental model.","authors":"Clelia Suriano, Onofrio Daniele Terrevoli, Francesco Staffieri, Luca Lacitignola, Antonio Crovace, Luisa Pellicani, Michela Taurino, Silvia Colucci, Maria Grano, Alberto Maria Crovace, Graziana Colaianni","doi":"10.1093/jbmrpl/ziag057","DOIUrl":"10.1093/jbmrpl/ziag057","url":null,"abstract":"<p><p>Scientific evidence has demonstrated the involvement of irisin, a molecule produced by muscle contraction, in preventing the onset of musculoskeletal decline. We previously demonstrated that the expression of irisin and its muscle-derived precursor FNDC5 is affected by unloading in skeletal muscle of hindlimb-unloaded (HU) mice. Studies in the HU mouse model showed that treatment with irisin prevents muscle wasting and atrophy. In parallel, human studies documented a strong association between irisin/FNDC5 and muscle function. Therefore, the scientific community is committed to determining whether irisin may represent a promising clinical strategy for preventing and treating disorders caused by muscle inactivity, such as those affecting bedridden or elderly patients. In translational research from mice to humans, there are very few in vivo studies conducted on large animals. The sheep model is an excellent model for studying the musculoskeletal system due to its anatomical characteristics, which share similarities with humans, allowing for the reproduction of mechanical load distribution on the limbs. To provide translational knowledge on the progression of muscle atrophy, we evaluated the impact of unloading on the expression of FNDC5 and functional proteins of skeletal muscle in sheep. Our findings revealed a reduction of FNDC5 in the quadriceps muscle after 2 wk of immobilization. The FNDC5 decrease is accompanied by a reduction of myosin isoforms <i>MyHC1</i> and <i>MyHC2x</i>, and an increase in muscle fibrosis. Importantly, FNDC5 expression positively correlated with expression of myosins, implying that the irisin/FNDC5 system is a driving force for muscle function in this large animal model.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag057"},"PeriodicalIF":3.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive profiling of the competitive interplay among carbamylation, glycation, and enzymatic cross-links in human bone.","authors":"Shoutaro Arakawa, Shota Katayama, Hikari Sugawa, Taiki Neyatani, Yu Yamashita, Daisuke Kubota, Tomohiro Kayama, Hiroteru Hayashi, Teruyuki Miyasaka, Toshiyuki Omori, Ryoji Nagai, Mitsuru Saito","doi":"10.1093/jbmrpl/ziag056","DOIUrl":"10.1093/jbmrpl/ziag056","url":null,"abstract":"<p><p>Carbamylation-derived products (CDPs) are implicated in protein dysfunction but remain understudied in human bone. We profiled homocitrulline (HCit, the predominant CDP), advanced glycation end-products (AGEs), and enzymatic cross-links in human cancellous bone specimens (<i>n</i> = 211). Homocitrulline accumulated substantially, surpassing carboxymethyl-lysine. Multivariable regression identified male sex and blood urea nitrogen (BUN) as independent determinants of HCit. This suggests men face a \"dual burden\" of renal-dependent accumulation and physiological urea loading driven by greater muscle mass. We observed a shift in the modification balance where higher BUN increased the HCit fraction while decreasing the AGEs-HCit ratio. Functionally, HCit correlated negatively with immature cross-links. Crucially, partial coefficient of determination (R²) analysis revealed that carbamylation and glycation act as concurrent determinants of cross-link impairment, with HCit exerting a stronger inhibitory effect than AGEs specifically in patients with mild BUN elevation (≥21 mg/dL). These findings demonstrate that carbamylation is a pervasive modification that actively interferes with collagen maturation, posing a significant threat to bone quality even in non-dialysis populations. Monitoring the carbamylation-glycation balance may offer new insights into bone fragility, especially in aging men and early-stage CKD.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag056"},"PeriodicalIF":3.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of leucine-enriched essential amino acid supplementation combined with different exercise regimen on appendicular skeletal muscle mass and muscle performance in older adults: an open label randomized controlled trial.","authors":"Chintrai Thavonlun, Jirawat Limsapjaroen, Praesiri Yoosuk, Chantas Mahaisavariya","doi":"10.1093/jbmrpl/ziag052","DOIUrl":"10.1093/jbmrpl/ziag052","url":null,"abstract":"<p><p>Sarcopenia in older adults increases fall risk and frailty. Improving muscle mass and function enhances balance and supports basic activities of daily living. Leucine-enriched essential amino acid supplementation combined with resistance training has been shown to enhance muscle performance. The present study evaluated muscle performance outcomes after 6 mo of these treatments. In an open-label randomized controlled trial, 66 participants were randomized equally to control and intervention groups (<i>n</i> = 33 each). Both groups consumed daily leucine-enriched essential amino acid supplements after exercise. The intervention group performed resistance training, and the control group followed regular walking and strengthening exercises. Primary outcomes were appendicular skeletal muscle mass index (ASMI), gait speed, and hand grip strength. Safety was assessed by adverse event reporting and laboratory tests. The results of this study show no significant improvement in ASMI in either group after 6 mo. Both groups demonstrated significant gait speed improvements, with no between-group difference. Hand grip strength improved only in the non-dominant hand of the control group. No serious adverse events occurred, and kidney function remained stable. In conclusion, 6 mo of daily leucine-enriched essential amino acid supplementation combined with exercise did not increase ASMI among healthy older adults. Gait speed showed a positive association with supplementation and daily exercise regardless of regimen. Improvement in hand grip strength was observed only in the non-dominant hand, warranting further investigation to clarify the effect of supplementation combined with exercise. Additional clinical studies are required to establish the effectiveness of this regimen in preserving muscle mass and enhancing functional performance. <b>Clinical trial registration:</b> This study has been registered with the Thai Clinical Trials Registry (ID: TCTR20210824002).</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag052"},"PeriodicalIF":3.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of contrast on opportunistic computed tomography vertebral bone mineral density analysis using internal calibration.","authors":"Bryn E Matheson, Kirsten N Bott, Andrew G Kiraly, Richard E A Walker, Steven K Boyd, Sarah L Manske","doi":"10.1093/jbmrpl/ziag053","DOIUrl":"10.1093/jbmrpl/ziag053","url":null,"abstract":"<p><p>Opportunistic CT, which repurposes clinical CT scans, has the potential to aid in osteoporosis screening and diagnosis. To convert CT scans to bone-equivalent densities without a calibration phantom, internal (or phantomless) calibration methods have been developed, using referent tissues of known density within the body. A key limitation is that intravenous iodinated contrast enhancement, which is routinely used in clinical settings, impacts quantitative measurements derived from these phantomless calibration techniques. Therefore, this cross-sectional study examined the influence of contrast enhancement on internal reference tissues and volumetric BMD (vBMD) measures derived using phantomless internal calibration. Hematuria protocol CT scans (<i>N</i> = 194) were retrospectively analyzed. This protocol included unenhanced and 2 enhanced CT scans from the nephrographic (~90 s delay) and urographic (~10 min delay) phases. The vertebrae were automatically identified and segmented with labels for the vertebral body and trabecular bone compartment in the third lumbar vertebra. Internal density calibration was performed using our previously established method with internal referent tissues (air, adipose, skeletal muscle, and cortical bone) to estimate the effective energy of each scan. A linear correction, derived based on training data from the nephrographic phase, was applied to test datasets from both the nephrographic and urographic phases. The nephrographic phase increased the vertebral body vBMD by 9.90 ± 4.28 mg/cm³ (5.52%, <i>p</i> < .0001) and the urographic phase by 2.33 ± 3.26 mg/cm³ (1.33%, <i>p</i> < .0001) compared to unenhanced scans. Applying the linear equation derived from the nephrographic training data reduced vBMD differences in the nephrographic test data but increased the variation in the urographic phase vBMD, demonstrating the need for phase-specific correction. This study demonstrates that vBMD measurements from contrast-enhanced CT are subject to significant error unless the interval between contrast administration and scan acquisition can be accounted for.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag053"},"PeriodicalIF":3.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved segmentation accuracy in high-resolution peripheral quantitative computed tomography scans of carpal bones using adaptive local thresholding.","authors":"Michael T Kuczynski, Simone Poncioni, Sarah Elmahdy, Erica Baldesarra, Philippe Zysset, Sarah L Manske, Danielle E Whittier","doi":"10.1093/jbmrpl/ziag054","DOIUrl":"10.1093/jbmrpl/ziag054","url":null,"abstract":"<p><p>The choice of segmentation method for HR-pQCT scans influences accuracy of bone microarchitecture measurements. Smaller or under-mineralized bone can present challenges in accurate extraction of bone structure using global thresholding methods, as local variations in intensity are not considered and finer structural details are not detected. This is especially important in small hand bones, where bone structure is finer, or younger populations, where bone tissue may be under mineralized. This study compared accuracy of global thresholding methods using Gaussian and Laplace-Hamming filters, and an adaptive local thresholding (AT) method in HR-pQCT scans of carpal bones. Eight ex vivo human cadaveric forearms (<i>n</i> = 64 carpal bones) were analyzed. Three specimens (<i>n</i> = 24 carpal bones, 2 female, mean age: 82.7 ± 4.6 yr) were used for AT parameter optimization, and 5 specimens (<i>n</i> = 40 carpal bones, 3 female, mean age: 82.0 ± 6.4 yr) were used to compare trabecular microarchitecture accuracy and spatial agreement relative to micro-CT (μCT, 20 μm isotropic resolution). Micro-CT images were segmented using a Gaussian filter and Otsu's method, and HR-pQCT images were segmented using Gaussian filtering and global thresholding, Laplace-Hamming filtering and global thresholding, and the AT method. Trabecular thickness (Tb.Th), separation (Tb.Sp), and bone volume fraction (Tb.BV/TV) accuracy were evaluated, and spatial agreement was assessed using Dice similarity coefficients (DSC), 95th percentile Hausdorff distances (HD95), and average symmetric surface distances (ASSD). The AT method yielded the smallest absolute and relative errors, and lowest bias across all trabecular parameters. Compared to the Gaussian and fixed threshold method, AT reduced mean absolute error by 36% for Tb.Th, 14% for Tb.Sp, and 15% for Tb.BV/TV, and achieved the highest spatial agreement with μCT (DSC = 0.84, HD95 = 0.061 mm, and ASSD = 0.018 mm). These findings extend prior HR-pQCT segmentation validation studies to carpal bones and demonstrate that AT outperforms the standard and Laplace-Hamming methods.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 6","pages":"ziag054"},"PeriodicalIF":3.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular characterization of familial hypocalciuric hypercalcemia in an endocrine practice: a case series of 25 patients.","authors":"Jack Lin, Tracy S Wang, Amy Donahue, Joseph L Shaker","doi":"10.1093/jbmrpl/ziag049","DOIUrl":"10.1093/jbmrpl/ziag049","url":null,"abstract":"<p><p>Familial hypocalciuric hypercalcemia (FHH) is a disorder caused by abnormal sensing of calcium by the parathyroids and renal tubules and may mimic primary hyperparathyroidism (PHPT). Patients with FHH should not be subjected to unnecessary and potentially harmful parathyroid surgery. We sought to evaluate the clinical and biochemical presentation of FHH in our endocrine practice. This was a retrospective chart review done after Institutional Review Board approval. We describe 25 cases of likely FHH from our endocrine practice (20 FHH1, 1 FHH2, and 4 FHH3). The 24-h urinary calcium levels were often greater than 100 mg/24 h and sometimes greater than 200 mg/24 h. The calcium to creatinine clearance ratio (CCCR) was consistently <0.01 in 10 of 22 (45%). We also describe several variants of <i>CASR</i> and 1 variant of <i>GNA11</i> that are probably pathogenic. Some patients, particularly FHH3 patients, have hypercalcemia severe enough to warrant treatment with a calcimimetic medication (cinacalcet). Traditional methods of excluding FHH using 24-h urinary calcium and CCCR are not adequate to distinguish FHH and PHPT. In addition to young age, family history of hypercalcemia and low CCCR, we believe molecular testing should be considered prior to surgery when hypercalcemia cannot be demonstrated to be acquired and in the case of persistent PHPT after surgery by an experienced parathyroid surgeon.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag049"},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing pain in polyostotic fibrous dysplasia/Mccune-albright syndrome patients: a pilot study.","authors":"Andrew Levitsky, Nicholas Madian, Alisa Johnson, Michelle Singh, Meera Deva, Alison M Boyce, M Catherine Bushnell, Eleni Frangos","doi":"10.1093/jbmrpl/ziag045","DOIUrl":"10.1093/jbmrpl/ziag045","url":null,"abstract":"<p><p>Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare skeletal disorder associated with significant pain and symptom burden. Pain in FD/MAS has been predominantly attributed to bone fracturing or fibrous tissue changes within the skeletal system. However, recent evidence indicates that factors beyond skeletal disease burden may contribute to pain in FD/MAS, including central nervous system alterations. Further, the type of pain experienced by patients (eg, constant, flare, radiating, and local) has yet to be fully characterized, limiting the development of individualized treatment approaches. In this pilot study, we examined the associations between bone lesions detected using sodium fluoride F18 [¹⁸F-NaF] PET/CT scans and self-reported pain in 14 patients with FD/MAS. All participants completed body pain maps and questionnaires regarding pain and symptom burden. Bone turnover markers (eg, osteocalcin, alkaline phosphatase, and N-terminal telopeptidase [NTx]) were also evaluated in relation to pain. Contrary to the previously described characterization of FD/MAS pain as persistent background pain with occasional flares, only 38% of the current sample described pain as \"persistent pain with pain attacks.\" Patients also described pain as \"persistent with slight fluctuations\" (31%), \"pain attacks with pain between them\" (23%), and \"pain attacks without pain between them\" (8%). Patients reported pain across multiple body sites. Neither background pain nor flare pain were reliably associated with skeletal burden scores or bone lesions in our sample. The presence of bone lesions in FD/MAS may not provide sufficient evidence to predict pain. Other factors, including the size or number of bone lesions, as well as other skeletal abnormalities, may also contribute to the pain experience. Future phenotyping efforts in FD/MAS are needed to better understand peripheral and central nervous system contributions that may lead to improved therapeutic strategies.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 5","pages":"ziag045"},"PeriodicalIF":3.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}