Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic disorder, characterized by fibroblast growth factor 23 (FGF23)-mediated renal phosphate wasting and impaired bone mineralization. Iron deficiency in ADHR increases FGF23 production and can worsen hypophosphatemia. Evidence to guide optimal management in severe adult cases remains limited. We report the use of burosumab as bridging therapy in a 19-yr-old woman with genetically confirmed ADHR (FGF23 p.Arg176Trp), severe osteomalacia, iron-deficiency anemia, and a low-energy femoral diaphyseal fracture complicated by nonunion despite conventional therapy. Treatment with burosumab resulted in rapid clinical improvement, with marked reduction in musculoskeletal pain and stiffness, and restoration of independent ambulation within four months. BMD increased substantially (+11.7% at the LS and +14.2% at the total hip at 5 mo; +63.8% and +55.5% from baseline at approximately 11 mo, respectively), while trabecular bone score remained within the normal range, a pattern consistent with improved mineralization and preserved trabecular texture. Serum phosphate increased but did not consistently normalize at trough, prompting dose escalation. At 8 mo, the burosumab dose was increased to 50 mg (1.25 mg/kg) due to persistent hypophosphatemia; with concurrent oral iron replacement, transient hyperphosphatemia (1.61 mmol/L) occurred and was managed by delaying the next dose by 14 d and reducing the dose back to 1 mg/kg. The patient also underwent additional surgical intervention, which may have contributed to the overall outcome; radiographic callus formation was evident 5 mo post-surgery. To our knowledge, this is the first full-length report describing burosumab use in genetically confirmed ADHR with longitudinal biochemical and densitometric follow-up, and it highlights the importance of careful monitoring of phosphate and iron indices when combining therapies.

Tumor-induced osteomalacia (TIO) is a rare syndrome caused by FGF23-secreting phosphaturic mesenchymal tumors (PMTs). Clinicians frequently misdiagnose mandibular PMTs due to their histological mimicry of giant cell lesions. We report a 16-year-old female with mandibular PMT-induced TIO who endured a 5-year diagnostic delay across eight hospitals. Two factors confounded her diagnosis: histological mimicry of giant cell reparative granuloma and an incidental SMARCAL1 variant misdirecting clinical attention toward a genetic disorder. Ultimately, integrated histopathologic evaluation and focal FGF23 immunohistochemistry supported the diagnosis of PMT, with serum P1NP reaching 435.00 ng/mL and β-CTX exceeding 6.00 ng/mL at peak disease severity, while [18]F-AlF-NOTA-TATE PET/CT localized the lesion. Tumor resection with fibula free flap reconstruction achieved early postoperative improvement in serum phosphate levels and symptoms, although long-term clinical, biochemical, and radiographic follow-up remains necessary to assess durable remission and monitor for recurrence. This case illustrates multiple diagnostic pitfalls in TIO with mandibular PMT, emphasizing that a high index of suspicion and integration of biochemical, histological, and imaging findings are essential to avoid delayed diagnosis.

X-linked hypophosphatemia (XLH) is a hereditary phosphate-wasting disorder that progressively impairs mobility, physical functioning and quality of life. Although physical activity (PA) can improve physical functioning for common comorbidities of XLH, such as osteoarthritis, its effects in individuals with XLH are not understood. The objective of our study was to understand how XLH impacts the experience of participating in PA and to identify barriers to and facilitators of PA specific to people with XLH. To complete our objective, we conducted semi-structured qualitative interviews with adults diagnosed with XLH. Data was analyzed using reflexive thematic analysis. 17 adults (2 male) participated, and we identified four main themes: (1) people living with XLH are unable to or are uncomfortable participating in impact exercise; (2) excessive physical activity causes fatigue and exacerbates pain and stiffness; (3) exercise as a tool to improve symptoms of XLH and function in the long term; (4) strategizing movement and tailoring exercise is essential to exercise participation. We identify two potential intervention directions leveraging identified facilitators to address the reported barriers: (1) education on pacing designed to help individuals with XLH manage fatigue and pain; (2) a continuing education resource designed to help exercise providers tailor exercise for individuals with XLH. Future research should focus on understanding PA in XLH to inform the development of feasible and appropriate interventions. In addition, improving understanding of the pathophysiology of consequences such as osteomalacia, OA, and enthesopathies may help clarify risks associated with PA and XLH.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF23) secreting phosphaturic mesenchymal tumors. We report a 53-year-old man with progressive osteomalacia resulting in bedridden status. Renal phosphate wasting despite normal vitamin D, intact parathormone, and renal function raised suspicion of TIO, confirmed by elevated FGF23. However, the occult tumor was localized only by Ga-68 DOTANOC wholebody PET-CT, highlighting the diagnostic challenges in TIO.

A woman in her thirties presented with progressive bone pain, muscle weakness, recurrent stress fractures, and delayed fracture healing. Laboratory investigations demonstrated hypophosphatemia, renal phosphate wasting, elevated fibroblast growth factor 23 (FGF23), and inappropriately low 1,25-dihydroxyvitamin D, leading to a diagnosis of FGF23-mediated tumor-induced osteomalacia (TIO) approximately one year after symptom onset. Bone scintigraphy demonstrated multiple fractures involving the ribs and pubic bones. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) identified mild uptake in the left femoral head/femoral neck region, and targeted magnetic resonance imaging (MRI) confirmed a well-defined 6-mm lesion with low signal intensity on T1- and T2-weighted images and high signal intensity on short tau inversion recovery images. Somatostatin receptor scintigraphy (SRS) showed no abnormal uptake. Systemic venous sampling (SVS) demonstrated elevated FGF23 levels in the left pelvic venous drainage region. CT-guided biopsy revealed a phosphaturic mesenchymal tumor (PMT) with FGF23 immunohistochemical positivity. Complete resection would likely have required hemiarthroplasty or total hip arthroplasty because of the tumor location, and the patient declined surgery. Burosumab was therefore initiated. At 24 weeks, serum phosphate increased from 1.5 to 4.1 mg/dL, alkaline phosphatase decreased from 145 to 100 U/L, generalized bone pain and gait disturbance improved markedly, pseudofracture-related uptake disappeared on bone scintigraphy, and lumbar-spine and femoral-neck bone mineral density (BMD) improved. This case shows that multimodal localization can identify micro-TIO lesions that may escape conventional strategies, and that FGF23 blockade can be clinically effective in a localized FGF23-positive 6-mm PMT when surgery is anatomically challenging or declined.

Phosphaturic mesenchymal tumor (PMT) is an uncommon neoplasm and the leading cause of tumor-induced osteomalacia (TIO). We report a 55-year-old woman with a 2-year history of progressive hip pain and hypophosphatemia. Laboratory findings demonstrated renal phosphate wasting. Conventional imaging revealed a small soft-tissue nodule in the right thigh, and 18 F-AlF-NOTA-octreotide (18F-OC) PET/CT (positron emission tomography/computed tomography) showed intense radiotracer uptake, accurately localizing the culprit lesion. Surgical excision confirmed a PMT, and serum phosphate levels normalized postoperatively with resolution of symptoms. This case highlights the diagnostic value of 18 F-OC PET/CT in detecting small PMTs and underscores the importance of considering TIO in patients with persistent hypophosphatemia and unexplained musculoskeletal symptoms.

X-linked hypophosphatemia (XLH) is a progressive disease in which excess FGF23 causes renal phosphate wasting, leading to hypophosphatemia. Consequences in adults include osteomalacia, fractures, pseudofractures, joint dysfunction, pain, and impaired mobility. Treatments for XLH are the anti-FGF23 antibody burosumab and active forms of vitamin D alone or in combination with oral phosphate (Pi/D). Randomized studies comparing burosumab with Pi/D in adults with XLH are lacking. We present a 3-yr follow-up analysis evaluating real-world effectiveness of burosumab versus Pi/D based on biochemistry and standardized symptom assessments (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) using data from the XLH Disease Monitoring Program (DMP; NCT03651505), a prospective, Americas-based study. Adults with XLH initiated burosumab between baseline and the year 1 visit (N = 54) or reported being on Pi/D therapy at enrollment (N = 55) were included. After adjusting for baseline differences using inverse probability of treatment weighting, the data showed a significantly higher mean (SD) change from baseline in serum phosphate with burosumab versus Pi/D (year 1: 0.8 [0.8] vs 0.1 [0.7] mg/dL; year 3: 0.6 [0.8] vs 0.1 [0.7] mg/dL, both p < .001). A higher proportion of burosumab versus Pi/D participants achieved serum phosphate levels above the lower limit of normal (2.5 mg/dL; year 1: 70.5% vs 18.8%; year 3: 60.8% vs 25.0%, both p < .001). At year 1, changes from baseline in WOMAC pain (-6.3 [27.7] vs 2.1 [22.4], p = .055), physical function (-6.4 [19.1] vs 0.1 [29.0], p = .122), and stiffness (-11.1 [32.1] vs -2.3 [33.7], p = .073) were not statistically significant between cohorts, but were significant at year 3 (pain: -9.8 [22.6] vs 3.3 [24.1], p < .001; physical function: -10.0 [25.7] vs 3.3 [24.7], p = .001; stiffness: -15.2 [29.5] vs -3.7 [31.4], p = .016). In this real-world analysis of adults with XLH over a 3-yr follow-up, burosumab treatment was associated with improved serum phosphate and patient-reported outcomes versus Pi/D.

The threshold for vitamin D deficiency is mainly based on osteomalacia prevention. Osteomalacia is diagnosed by bone biopsy, but may potentially also be identified biochemically. Our objective was to examine the prevalence of exploratory biochemical patterns compatible with osteomalacia in a population with low vitamin D status, as well as the effect of vitamin D supplementation on the biochemical parameters. The study was cross-sectional followed by a randomized controlled trial (trial registration number: NCT02750293). The participants were recruited from the population-based Tromsø study. Plasma parathyroid hormone, serum calcium, alkaline phosphatase and bone-specific alkaline phosphatase were measured. 423 participants were included in the cross-sectional part and 382 completed the randomized controlled trial (194 given vitamin D (100,000 IU as a loading dose followed by 20,000 IU per week for four months) and 188 given placebo). The mean serum 25-hydroxyvitamin D level in the cohort was 34 nmol/L. None of the participants had a combination of high (above reference range) serum parathyroid hormone, high alkaline phosphatase, and low (below reference range) serum calcium. With the most permissive exploratory biochemical pattern the prevalence was 8.3%. In the intervention study vitamin D significantly reduced plasma parathyroid hormone and alkaline phosphatase and increased serum calcium as compared to placebo. In conclusion, the prevalence of the explored biochemical patterns compatible with ostemalacia was low and strongly dependent on the analytical thresholds applied. In the absence of validation against bone histomorphometry, these findings cannot determine the prevalence of osteomalacia or establish an appropriate serum 25OHD threshold.

Tumor-induced osteomalacia is a rare acquired disorder of phosphate metabolism caused by fibroblast growth factor (FGF)23-secreting mesenchymal tumors. We report the case of a 39-year-old man with a 3-year history of progressive musculoskeletal pain, in whom unrecognized hypophosphatemia led to misdiagnoses, including osteoporosis and inflammatory musculoskeletal disorders, and consequently, to inappropriate management. Biochemical evaluation revealed persistent hypophosphatemia, elevated alkaline phosphatase levels, secondary hyperparathyroidism, and markedly increased serum FGF23 levels. Gallium-68 DOTATATE positron emission tomography/computed tomography (PET/CT) identified a phosphaturic mesenchymal tumor located in the medial condyle of the right distal femur, which was subsequently confirmed histopathologically after surgical excision. Following surgery, serum phosphorus and FGF23 levels rapidly normalized, accompanied by significant clinical improvement. This case highlights unrecognized hypophosphatemia as a critical yet preventable cause of diagnostic delay and emphasizes the importance of routine serum phosphate assessment to avoid misdiagnosis and enable timely curative treatment.

Rheumatoid arthritis (RA) is the most common chronic inflammatory arthritis and a leading cause of disability worldwide. However, several diseases may mimic RA, particularly in patients presenting with polyarticular pain or seronegative inflammatory arthritis. Misdiagnosis may result in inappropriate immunosuppressive therapy and delayed treatment of the underlying disease. Recognizing these mimickers remains a critical challenge in rheumatology practice. We conducted a retrospective case series of patients evaluated at a tertiary rheumatology center between January 2021 and December 2025. Patients presenting with clinical features suggestive of RA but subsequently diagnosed with alternative conditions were included. Clinical presentation, laboratory findings, imaging studies, diagnostic reasoning, and treatment outcomes were reviewed. Five patients initially suspected to have RA were ultimately diagnosed with alternative conditions. These included ferric carboxymaltose-induced hypophosphatemic osteomalacia, calcific tendinitis, polyarticular gout, remitting seronegative symmetrical synovitis with pitting edema (RS3PE) associated with malignancy, and carcinomatous polyarthritis secondary to colon adenocarcinoma. Several diagnostic clues including atypical joint involvement, abnormal laboratory findings, imaging abnormalities, and systemic symptoms helped establish the correct diagnoses. RA mimickers represent an important diagnostic challenge in rheumatology practice. Crystal arthropathies, metabolic bone diseases, calcific tendinitis, and paraneoplastic syndromes may closely resemble RA. Awareness of atypical clinical features and recognition of diagnostic red flags are essential for accurate diagnosis. Early identification of these conditions allows appropriate treatment and prevents unnecessary exposure to immunosuppressive therapies.

SUNFLOWER is a 10-year longitudinal observational cohort study of patients with X-linked hypophosphatemia (XLH) in Japan and South Korea. This report describes the 3-year cut-off of SUNFLOWER, including data from 1 year of burosumab administration (burosumab-treated group) and 1 year after providing informed consent (non-burosumab-treated group). The real-world effectiveness of burosumab and the associations between bone metabolism markers and quality of life (QoL)/patient-reported outcomes (PROs) and rickets severity scores (RSS)/height over 1 year in burosumab-treated patients with XLH were assessed. As burosumab had not been launched in South Korea at the time of cut-off, data from South Korea were not available. The main outcome measures were changes in serum parameters, and correlations between alkaline phosphatase (ALP) levels and RSS and height (children), and between ALP (children) or bone-specific ALP (BALP; adults) levels and QoL/PROs and motor functions. In total, 146 patients were enrolled, including 69 (47.3%) children and 77 (52.7%) adults. After 1 year of treatment, burosumab-treated patients (43 [62.3%] children, 29 [37.7%] adults) had improved serum phosphate levels, 1,25-dihydroxyvitamin D, and ALP/BALP compared with pre-treatment levels. In children, RSS changes significantly correlated with ALP changes (correlation coefficient: 0.806, p < 0.001), but height changes did not show significant correlation. There were no significant correlations between changes in ALP/BALP and QoL/PRO assessments or motor function. In conclusion, decreased ALP correlated with an improvement in rickets severity score in Japanese children with XLH, suggesting that ALP may be a useful marker for monitoring both the severity and improvement of rickets/osteomalacia.