Abstract Niclosamide, known for its anticancer and anti-inflammatory effects via modulation of NF-κB and STAT3 signaling, has now been shown to suppress osteoclast differentiation and function through STAT3 inhibition. In vitro experiments demonstrated that niclosamide downregulates STAT3 activation, leading to reduced expression of genes involved in osteoclast differentiation, acid secretion, chemotaxis, and pyroptosis, thereby impairing multiple osteoclast biological behaviors. In vivo, niclosamide treatment attenuated bone loss in an ovariectomy-induced mouse model of osteoporosis by inhibiting osteoclast activity. The STAT3 activator colivelin partially reversed these niclosamide-induced effects on bone metabolism. Collectively, niclosamide inhibits both osteoclast formation and the bone-resorptive function of mature osteoclasts via suppression of the STAT3 pathway, suggesting a novel therapeutic approach for osteoporosis.
Abstract Anabolic steroids are increasingly explored for the management of musculoskeletal disease. Physiological testosterone levels support joint health, and supraphysiological levels of testosterone are linked to increased intervertebral disc (IVD) height and reports of vertebral endplate hyperconcavity. The ability of high-dose testosterone to modulate joint repair or degeneration remains speculative. The goal of this study was to determine if supraphysiological doses of testosterone promote IVD repair or alter the progression of age-associated IVD degeneration or knee osteoarthritis (OA) in the mouse. To assess injury repair, a percutaneous caudal IVD puncture was implemented at Co7/Co8 in 16.5-month-old male CD-1 mice (N=8/group). The lumbar spines of these mice were uninjured to assess age-related IVD degeneration. Mice were treated weekly with 15 mg/kg of testosterone enanthate for 6 weeks to emulate anabolic steroid use. Changes to IVDs and vertebral bones were assessed using microCT and histopathology, and the severity of knee OA was assessed by histopathology. In the caudal spine, loss of disc height induced by IVD puncture was partially rescued by testosterone with histological features associated with repair. In the lumbar spine, testosterone induced subchondral bone loss within the vertebral bodies, increased disc height, and promoted endplate hyperconcavity. Knee histopathology revealed severe OA by 18 months of age, irrespective of treatment. These findings highlight context-dependent effects of testosterone at doses modelling anabolic steroid use. Testosterone rescued disc height loss following IVD injury in the tail but did not improve age-associated IVD degeneration or knee OA. In the lumbar spine, testosterone induced vertebral subchondral bone loss, and increased disc height associated with endplate hyperconcavity resembling radiographic changes described as codfish vertebrae associated with osteoporosis and prolonged steroid therapy. Taken together, these findings suggest that both the IVD and vertebral bone respond to supraphysiological testosterone, with important differences in injury and age-associated degeneration.
Abstract Burosumab provides treatment benefits in children with X-linked hypophosphatemia. However, children with low rickets severity (Rickets Severity Score <2) were excluded from a previous phase 3, multicenter, active comparator-controlled randomized clinical trial. This descriptive interim analysis of the prospective SUNFLOWER cohort study included 69 children with X-linked hypophosphatemia aged ≤13 yr at enrollment. The burosumab and non-burosumab groups included 48 and 65 participants, respectively, with some overlap due to switching. Longitudinal changes in height and biochemical parameters (overall and stratified by disease severity [Rickets Severity Score <2/≥2; alkaline phosphatase
Abstract X-linked hypophosphatemia (XLH) is a rare, lifelong disorder of renal phosphate wasting that typically presents in childhood with skeletal deformities, growth retardation, and functional impairment, although these features may be less pronounced in milder cases. The disease persists into adulthood with chronic pain, mobility limitations, and psychosocial challenges. While pediatric XLH has been well described internationally, the lifelong disease journey in Taiwan remains poorly characterized. We conducted a multicenter qualitative study using semi-structured, in-depth interviews between July 2024 and January 2025 at 3 major medical centers, enrolling 15 patients with a clinical diagnosis of XLH (genetically confirmed in a subset): 8 pediatric patients (aged ≥5 yr) interviewed with caregivers and 7 adults interviewed independently. Interviews (~60 min) explored diagnostic pathways, treatment experiences, disease burden, and support needs; transcripts were analyzed thematically. Participants commonly reported delayed or missed diagnosis, with early symptoms such as bowed legs and short stature often misattributed to nutritional or growth-related issues, leading to late referral to specialist care. Oral phosphate supplementation and active vitamin D (Pi/D) were the predominant treatments; however, frequent dosing, poor palatability, and gastrointestinal side effects contributed to low adherence. Many adults had discontinued therapy, and 12 patients underwent corrective limb surgery, mainly during childhood or adolescence. Across the life course, patients experienced chronic bone pain, reduced mobility, and insufficiency fractures, as well as psychosocial burdens, including anxiety, low self-esteem, social withdrawal, and caregiver stress, often compounded by guilt related to hereditary transmission. Patients and caregivers emphasized unmet needs in disease education, transition from pediatric to adult care, peer support, and interest in novel therapies, such as burosumab. These findings highlight substantial lifelong disease burden among patients with XLH in Taiwan and underscore the need for earlier diagnosis, multidisciplinary care, and improved access to emerging therapies.
Abstract Ossification of the posterior longitudinal ligament (OPLL) is increasingly recognized as a metabolic ossification phenotype characterized by obesity-related abnormalities, particularly visceral adiposity. Although visceral fat has been implicated in the development of OPLL, its relationship with ossification severity and multiligamentous involvement remains unclear. This study aimed to examine whether anthropometric indices reflecting central adiposity show consistent associations with the burden of spinal ligament ossification. We retrospectively analyzed 252 individuals, including 163 patients with OPLL and 89 controls. Anthropometric indices—body mass index (BMI) and body roundness index (BRI)—were evaluated alongside computed tomography (CT)-based measurements of visceral and subcutaneous fat areas. Ossification severity was quantified using a validated CT-based ossification index encompassing OPLL, ossification of the ligamentum flavum (OLF), ossification of the anterior longitudinal ligament (OALL), and ossification of the supra/interspinous ligaments (OSIL). Logistic regression, spline modeling, and sex-stratified analyses were performed. Patients with OPLL, particularly those with diffuse-type disease, exhibited significantly greater visceral adiposity and higher BMI and BRI values than controls. Both BMI and BRI were associated with the presence of diffuse OPLL, whereas their associations with localized OPLL were weaker. Nonlinear analyses showed that BMI was associated with ossification severity mainly within the lower BMI range, whereas BRI demonstrated generally linear associations across multiple ligamentous sites. These patterns were more evident in females. These findings suggest that anthropometric indices reflecting central adiposity may provide complementary information when evaluating the extent of spinal ligament ossification. While CT-derived visceral fat remains the direct measure of abdominal adiposity, indices such as BRI may offer additional context for understanding metabolic features associated with ossification burden in OPLL.
