High rate of progression to symptomatic multiple myeloma in patients with smoldering myeloma and isolated osteoporotic vertebral fracture.

Multiple myeloma (MM) frequently causes vertebral fractures (VF). Some are lytic lesions and others have the aspect of benign osteoporotic fractures not requiring anti-myeloma treatment. We explored outcome of these patients with smoldering myeloma (SM) and osteoporotic VF. In this retrospective bi-centric study, patients were identified using a systematic keyword search on electronic medical records. Patients with SM and isolated VF of osteoporotic aspect without indications for myeloma-specific therapy were included. Overall, 13 (7 %) of the 184 identified patients had SM and VF confirmed to be osteoporotic (median number of VF was 3). During follow-up, 12 (92 %) patients evolved to symptomatic MM, 7 (54 %) of them within 18 months (early progressors). Myeloma defining events were new lytic bone lesions in 7 patients (53.8 %). The serum calcium level was significantly higher in the early progressor group (median 2.35 IQR [2.31-2.38] and 2.28 IQR [2.21-2.29] respectively, p = 0.003). Early progressors had a higher number of VF at diagnosis (3.0 [2.0-5.5] vs 1.0 [1.0-2.5], p = 0.18) and more frequently evolved to symptomatic MM because of lytic bone lesions (5 [71 %] vs 2 [33 %], p = 0.13) compared to late progressors. VF of osteoporotic appearance in the context of SM is a rare situation but at high risk of rapid progression to symptomatic MM, suggesting that they may represent bone fragility linked to MM infiltration rather than solely osteoporotic fractures. Further studies are needed to assess if earlier treatment might be beneficial in this population.

Successful Burosumab Treatment in an Adult Patient with X-Linked Hypophosphatemia and Chronic Kidney Disease Stage 3b.

X-linked hypophosphatemic rickets (XLH) is a genetic cause of renal hypophosphatemia due to inactivation of the PHEX gene, with an inappropriate concentration of fibroblast growth factor 23 (FGF23). Burosumab, an anti-FGF23 monoclonal antibody, is a validated treatment for XLH, but its use in patients with chronic kidney disease (CKD) has not been validated. A 61-year-old man with XLH developed CKD during follow-up. Conventional treatment (phosphate salts and active vitamin D analogs) was poorly tolerated. Treatment with burosumab was decided at a multi-professional meeting. Before burosumab initiation, his measured glomerular filtration rate was 44 mL/min/1.73 m2 defining CKD stage 3b and intact FGF23 concentration was very high (4496.0 ng/mL, N: 22.7-93.1) due to both XLH and CKD. Severe hypophosphatemia was observed after the two first injections of burosumab at usual doses (1 mg/kg monthly) and concomitant discontinuation of the conventional treatment. After increasing the dose and reducing the interval between doses (1.3 mg/kg every three weeks) from the third injection, serum phosphate concentration normalized and remained around the lower limit of the normal range. A local cutaneous reaction was observed just after the second injection, but did not recur. We report for the first time the efficacy and good short-term tolerance of burosumab in a patient with XLH and CKD, subject to a higher dosage aimed at achieving a phosphatemia at the lower limit of the normal range.

Adult height improved over decades in patients with X-linked hypophosphatemia: a cohort study.

OBJECTIVES: The aim of this study is to analyze height after cessation of growth (final height [FH]) and its evolution over the last decades in X-linked hypophosphatemia (XLH) patients in France, as the data on natural history of FH in XLH are lacking. DESIGN: We performed a retrospective observational study in a large cohort of French XLH patients with available data on FH measurements. MATERIALS AND METHODS: We divided patients into 3 groups according to their birth year: group 1 born between 1950 and 1974, group 2 born between 1975 and 2000, and group 3 born between 2001 and 2006, respectively, and compared their FHs. RESULTS: A total of 398 patients were included. Mean FHs were the following: for group 1, -2.31 ± 1.11 standard deviation score (SDS) (n = 127), 156.3 ± 9.7 cm in men and 148.6 ± 6.5 cm in women; for group 2, -1.63 ± 1.13 SDS (n = 193), 161.6 ± 8.5 cm in men and 153.1 ± 7.2 cm in women; and for group 3, -1.34 ± 0.87 SDS (n = 78), 165.1 ± 5.5 cm in men and 154.7 ± 6 cm in women. We report a significant increase in mean FH SDS over 3 generations of patients, for both men and women (P < .001). Final height SDS in male (-2.08 ± 1.18) was lower than in female (-1.70 ± 1.12) (P = .002). CONCLUSION: The FH of XLH patients in France increased significantly over the last decades. Even though men's FHs improved more than women's, men with XLH remain shorter reflecting a more severe disease phenotype. While the results are promising, most patients with XLH remain short leaving room for improvement.

The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data.

BACKGROUND: X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient's lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry. RESULTS: The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults ≥ 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately - 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH. CONCLUSION: The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.

Real-World Effectiveness of Osteoporosis Medications in France: A Nationwide Cohort Study.

Although drugs for osteoporosis have been demonstrated to be effective in reducing fracture risk in placebo-controlled clinical trials, data on effectiveness in real-world practice is limited. Data from the French national health insurance claims database (SNDS) were used to follow five cohorts of women aged ≥55 years after initiating treatment for ≥6 months with either denosumab, zoledronic acid, oral bisphosphonates, raloxifene, or teriparatide in 2014-2016. Fracture incidence was compared within each cohort between the 3 months following initiation (baseline fracture risk) and the 12month, 18month, and 24 month postinitiation periods. Data are presented as incidence rate ratios (IRRs) with their 95% confidence intervals (CIs)s. Overall, 67,046 women were included in the denosumab cohort, 52,914 in the oral bisphosphonate cohort, 41,700 in the zoledronic acid cohort, 11,600 in the raloxifene cohort, and 7510 in the teriparatide cohort. The baseline vertebral fracture rate ranged from 1.74 per 1000 person years (‰PY) in the raloxifene cohort to 34.75‰PY in the teriparatide cohort, and the baseline hip fracture rate from 0.70‰PY in the raloxifene cohort to 10.52‰PY in the zoledronic acid cohort. Compared with the baseline fracture rate, vertebral fractures involving hospitalization were significantly reduced in the 3-24-month postinitiation period with denosumab (IRR 0.6; 95% CI, 0.5-0.7), zoledronic acid (IRR 0.4; 95% CI, 0.3-0.4), teriparatide (IRR 0.3; 95% CI, 0.2-0.5), and oral bisphosphonates (IRR 0.6; 95% CI, 0.4-0.8). Hip fracture incidence was reduced with denosumab (IRR 0.8; 95% CI, 0.6-0.9), but higher for oral bisphosphonates (IRR 1.7; 95% CI, 1.2-2.3); no significant change in hip fracture rate was observed for zoledronic acid, teriparatide, or raloxifene. A reduction in nonvertebral, non-hip fracture incidence was observed only in the denosumab cohort (IRR 0.8; 95% CI, 0.7-0.9). These findings indicate that treatment with osteoporosis drugs is effective in the real-world setting. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Anticipated effects of burosumab treatment on long-term clinical sequelae in XLH: expert perspectives.

X-linked hypophosphatemia (XLH) is a rare, progressive, genetic disease with multisystem impact that typically begins to manifest in early childhood. Two treatment options exist: oral phosphate in combination with active vitamin D ("conventional therapy") and a fully human monoclonal anti-FGF23 antibody, burosumab. The clinical benefit of conventional therapy in adults is limited, and poor tolerance and complications are common. Burosumab was first approved as a treatment for XLH in 2018 and its disease-modifying benefits in clinical trials in children suggest burosumab treatment could also alter the disease course in adults. Without long-term clinical data on multiple XLH-related sequelae available, the results of an elicitation exercise are reported, in which eight global experts in XLH posited how long-term treatment with burosumab is anticipated to impact the life course of clinical sequelae in adults with XLH. Based on their clinical experiences, the available evidence and their disease understanding, the experts agreed that some long-term benefits of using burosumab are likely in adults with XLH even if they have a misaligned skeleton from childhood. Burosumab treatment is anticipated to reduce the incidence of fractures and halt the progression of clinical sequelae associated with conventional therapy. While the trajectories for established dental abscesses are not expected to improve with burosumab treatment, dental abscess development may be prevented. Starting treatment with burosumab in childhood to increase the likelihood of an aligned skeleton and continuation into and throughout adulthood to maintain euphosphatemia may optimize patient outcomes, although future real-world investigation is required to support this hypothesis.

Development of Spinal Enthesopathies in Adults With X-linked Hypophosphatemia.

CONTEXT: Musculoskeletal complications are the main manifestations in adults with X-linked hypophosphatemia (XLH). Enthesopathy significantly impairs quality of life. OBJECTIVE: To identify the risk factors associated with the development and progression of spinal enthesopathies in adults with XLH. DESIGN AND SETTING: We conducted a retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism. PATIENTS: Adults XLH patients with 2 EOS® imaging performed at least 2 years apart at the same center between June 2011 and March 2022. The progression of enthesopathies was defined as a new enthesopathy at least 1 intervertebral level in patients with or without presence of enthesopathy at baseline. MAIN OUTCOME MEASURES: Demographic, treatment, PHEX mutation with the progression of enthesopathies. RESULTS: Fifty-one patients (66.7% of women, mean age 42.1 ± 13.4 years) underwent 2 EOS imaging with an average interval of 5.7 (± 2.31) years.Progression of spinal enthesopathies was observed in 27 (52.9%) patients. In univariate analysis, patients with a progression of spinal enthesopathies were significantly older (P < .0005), were significantly older at treatment initiation (P = .02), presented with dental complications (P = .03), received less frequently treatment during childhood with phosphate and/or vitamin D analogs (P = .06), and presented more frequently with hip osteoarthritis (P = .002) at baseline. In multivariate analysis, none of these factors was associated with a progression of spinal enthesopathies. CONCLUSION: This study confirms the high proportion of patients with a progression of spinal enthesopathies. Age seems to be the main factor associated with progression.

Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment.

OBJECTIVES: To report the impact of continued burosumab treatment on clinical laboratory tests of efficacy, patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia who continued from a 96-week phase 3 study into a 48-week open-label extension. METHODS: Eligible participants from the phase 3 study continued on the burosumab regimen received at the end of the phase 3 study for a further 48 weeks (n=31). Some (not all) received compassionate burosumab treatment between the two studies (a period of 6-18 months). The primary efficacy outcome was fasting serum phosphate concentration; secondary outcomes were serum 1,25 dihydroxyvitamin D concentration, renal phosphate reabsorption, PROs and ambulatory function. RESULTS: Improvements in fasting serum phosphate, serum 1,25 dihydroxyvitamin D and renal phosphate reabsorption at 96 weeks were maintained through the 48-week extension. Improvements were also maintained in stiffness and physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index, pain and fatigue endpoints measuring using the Brief Pain Inventory short-form and Brief Pain Inventory, respectively, and in ambulatory function (6-Minute Walk Test).A post-hoc exploratory analysis exploring outcomes in participants who discontinued burosumab treatment between the studies (n=7) and those who received at least one dose (n=23) indicated that the benefits of burosumab on clinical laboratory tests of efficacy, PROs and ambulatory function may be lost when treatment is interrupted but recover over time when treatment is reinstated. CONCLUSION: Continued treatment with burosumab appears necessary for sustained clinical benefit. TRIAL REGISTRATION NUMBERS: Phase 3: NCT02526160; open-label extension: NCT03920072.

Post-authorisation safety study of burosumab use in paediatric, adolescent and adult patients with X-linked hypophosphataemia: rationale and description.

Background: X-linked hypophosphataemia (XLH) is a rare, inherited, phosphate-wasting disorder that elevates fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D (1,25(OH)2D) synthesis. Disease characteristics include rickets, osteomalacia, odontomalacia, and short stature. Historically, treatment has been oral phosphate and 1,25(OH)2D supplements. However, these treatments do not correct the primary pathogenic mechanism or treat all symptoms and can be associated with adverse effects. Burosumab is a recombinant human immunoglobulin G1 monoclonal antibody against FGF23, approved for treating XLH in several geographical regions, including Europe and Israel. Burosumab restores normal serum phosphate levels, minimising the clinical consequences of XLH. Safety data on long-term treatment with burosumab are lacking owing to the rarity of XLH. This post-authorisation safety study (PASS) aims to evaluate the safety outcomes in patients aged >1 year. Methods: The PASS is a 10-year retrospective and prospective cohort study utilising data from the International XLH Registry (NCT03193476), which includes standard diagnostic and monitoring practice data at participating centres. The PASS aims to evaluate frequency and severity of safety outcomes, frequency and outcomes of pregnancies in female patients, and safety outcomes in patients with mild to moderate kidney disease at baseline, in children, adolescents and adults treated with burosumab for XLH. It is expected that there will be at least 400 patients who will be administered burosumab. Results: Data collection started on 24 April 2019. The expected date of the final study report is 31 December 2028, with two interim reports. Conclusion: This PASS will provide data on the long-term safety of burosumab treatment for XLH patients and describe safety outcomes for patients receiving burosumab contrasted with those patients receiving other XLH treatments, to help inform the future management of XLH patients. The PASS will be the largest real-world safety study of burosumab. Registry identification: The International XLH Registry is registered with clinicaltrials.gov as NCT03193476 (https://clinicaltrials.gov/ct2/show/NCT03193476), and the PASS is registered with the European Union electronic Register of Post-Authorisation Studies as EUPAS32190 (http://www.encepp.eu/encepp/viewResource.htm?id=32191).

Efficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study.

The anti-fibroblast growth factor 23 monoclonal antibody burosumab corrects hypophosphatemia in adults with X-linked hypophosphatemia (XLH) and improves pain, stiffness, physical function, and fatigue. This post hoc subgroup analysis used data from the 24-week placebo-controlled period of a phase 3 study in 134 adults with XLH (ClinicalTrials.gov NCT02526160), to assess whether the benefits of burosumab are evident in 14 clinically relevant subgroups defined by baseline demographic and functional criteria, including sex, Brief Pain Inventory-short form (BPI-SF) Average And Worst Pain, region, race, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Stiffness, Physical Function and Pain domains and total score, use of opioid/other pain medication, active fractures/pseudo-fractures, and 6-min walk test distance. There were no statistically significant interactions between any of the subgroups and treatment arm for any endpoint. Higher proportions of subjects achieved mean serum phosphate concentration above the lower limit of normal (the primary endpoint) with burosumab than with placebo in all subgroups. For the key secondary endpoints (WOMAC Stiffness and Physical Function; BPI-SF Worst Pain) individual subgroup categories showed improvements with burosumab relative to placebo. For additional efficacy endpoints, burosumab was favored in some subgroups but differences were not significant and confidence intervals were wide. For some endpoints the treatment effect is small at 24 weeks in all subjects. This subgroup analysis shows that burosumab was largely superior to placebo across endpoints in the 14 clinically relevant subgroup variables at 24 weeks and is likely to benefit all symptomatic adults with active XLH.

Does delayed weight bearing in the surgical management of fractures of the upper end of the femur in the elderly lead to more complications? A prospective study.

INTRODUCTION: Fractures of the upper end of the femur (FUEF) lead to increased mortality and dependence in the elderly. However, mechanical complications after surgery persist in up to 20% of cases, which may justify a delayed resumption of full weight bearing to protect the osteosynthesis during consolidation. HYPOTHESIS: Our hypothesis was that the late resumption of weight bearing in an elderly population after a FUEF would be limited by a higher frequency of medical complications. METHODS: This was a prospective monocentric study including patients aged 80 or over with an isolated FUEF requiring osteosynthesis. The operator decided on the discharge. The primary endpoint was to show a difference in a medical complication score created for this study (APRETAR), between a group with, and a group without, weight bearing delayed by 45 days. RESULTS: Between 2016 and 2019, 254 patients (88±5.6 years, 77.6% women) were included, and of these, 70 (27.6%) had delayed weight bearing. The mean APRETAR at 45 days was greater in the delayed weight bearing group (5.9±8.6 vs. 5.7±11.0; p<0.001). One-year mortality was 12.6% (32 patients), with no difference between the two groups (p=0.51). The level of dependence was significant (IADL at 2.2±1.7), with some comorbidities (Charlson at 2.9±2.2 and CIRS-G at 6.5±4.3) and all comparable across the two groups but with low cognitive levels, especially in the group with delayed weight bearing (MMSE 15.9±10.7 vs. 21±6.9; p<0.001). CONCLUSION: This prospective study shows that delaying weight bearing in the elderly population, even for mechanical problems with FUEF, statistically increases medical complications but in a clinically acceptable manner. LEVEL OF EVIDENCE: II, Prospective cohort study.

Barriers and Expectations for Patients in Post-Osteoporotic Fracture Care in France: The EFFEL Study.

OBJECTIVES: This study aimed to quantify the relative importance of barriers to better secondary prevention of osteoporotic fractures and of care expectations expressed by patients with osteoporotic fractures in France. METHODS: A qualitative exploration of potential barriers to care and expectations was undertaken through a systematic literature review and in-depth patients interviews. A list of 21 barriers and 21 expectations was identified. These were presented to 324 subjects with osteoporotic fractures, identified in a representative sample of the French population, in the form of best-worst scaling questionnaires. Patients rated the relative importance of the attributes, and arithmetic mean importance scores were calculated and ranked. A Bayesian hierarchical model was also performed to generate a relative importance score. Latent class analysis was performed to identify potential subgroups of patients with different response profiles. RESULTS: A total of 7 barriers were rated as the most important, relating to awareness of osteoporosis and coordination of care. The highest-ranked barrier, "my fracture is not related to osteoporosis," was significantly more important than all the others (mean importance score 0.45; 95% confidence interval 0.33-0.56). A similar ranking of attributes was obtained with both the arithmetic and the Bayesian approach. For expectations, no clear hierarchy of attributes was identified. Latent class analysis discriminated 3 classes of respondents with significant differences in response profiles (the educated environmentalists, the unaware, and the victims of the system). CONCLUSIONS: Better quality of care of osteoporosis and effective secondary fracture prevention will require improvements in patient education, training of healthcare professionals, and coordination of care.

Evaluation of long-term TNFi effectiveness after a first switch in early axial spondyloarthritis considering time-varying prescription bias: an inverse-probability weighting analysis of the DESIR cohort.

OBJECTIVE: To evaluate long-term effectiveness of tumour necrosis factor inhibitor (TNFi) after a first switch, and their associated factors in an early axial spondyloarthritis (axSpA) population, considering time-varying prescription bias. METHODS: Observational prospective cohort (DEvenir des Spondylarthropathies Indifférenciées Récentes) with 5 years of follow-up, including 708 TNFi-naïve patients with early axSpA. Long-term effectiveness of TNFi after a first switch (ASAS40 response after at least 2 visits under treatment) were estimated using marginal structural models (implementing inverse-probability weighting and iterative propensity scores). Factors associated with the outcome were explored by multivariate Cox regression models. RESULTS: The hazard to present an ASAS40 response after a first TNFi switch was increased (HR=2.4 (95% CI 1.9 to 3.0)); this response ratio was slightly lower compared with the response in TNFi naïve patients after a first TNFi (HR=3.3 (95% CI 2.9 to 3.8)). HLA-B27 positive was the only factor independently associated with ASAS40 response after a first TNFi switch. CONCLUSION: After application of innovative methods to overcome time-varying prescription bias, the magnitude of the TNFi response after a first switch was found to be numerically lower but clinically relevant from the response in TNFi-naïve patients.

Osteogenesis Imperfecta: characterization of fractures during pregnancy and post-partum.

BACKGROUND: Pregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients. RESULTS: We conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth. We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group (p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group (p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score - 2.9 ± 1.6DS vs - 1.5 ± 1.7DS (p = 0.03), and total hip Z-score - 2.0 ± 0.7DS vs - 0.5 ± 1.4DS (p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant). CONCLUSIONS: OI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.

Prevalence of Enthesopathies in Adults With X-linked Hypophosphatemia: Analysis of Risk Factors.

CONTEXT: Enthesopathies are the determinant of a poor quality of life in adults with X-linked hypophosphatemia (XLH). OBJECTIVE: To describe the prevalence of patients with enthesopathies and to identify the risk factors of having enthesopathies. METHODS: Retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism between June 2011 and December 2020. Adult XLH patients with full body X-rays performed using the EOS® low-dose radiation system and clinical data collected from medical records. The main outcome measures were demographics, PHEX mutation, conventional treatment, and dental disease with the presence of enthesopathies. RESULTS: Of the 114 patients included (68% women, mean age 42.2 ± 14.3 years), PHEX mutation was found in 105 patients (94.6%), 86 (77.5%) had been treated during childhood. Enthesopathies (spine and/or pelvis) were present in 67% of the patients (n = 76). Patients with enthesopathies were significantly older (P = .001) and more frequently reported dental disease collected from medical records (P = .03). There was no correlation between the PHEX mutations and the presence of enthesopathies. Sixty-two patients had a radiographic dental examination in a reference center. Severe dental disease (number of missing teeth, number of teeth endodontically treated, alveolar bone loss, and proportion of patients with 5 abscesses or more) was significantly higher in patients with enthesopathies. CONCLUSION: Adult XLH patients have a high prevalence of enthesopathies in symptomatic adults patients with XLH seen in a reference center. Age and severe dental disease were significantly associated with the presence of enthesopathies.

Fully automated opportunistic screening of vertebral fractures and osteoporosis on more than 150 000 routine computed tomography scans.

OBJECTIVE: Osteoporosis is underdiagnosed and undertreated, although severe complications of osteoporotic fractures, including vertebral fractures, are well known. This study sought to assess the feasibility and results of an opportunistic screening of vertebral fractures and osteoporosis in a large database of lumbar or abdominal CT scans. MATERIAL AND METHODS: Data were analysed from CT scans obtained in 35 hospitals from patients aged 60 years or older and stored in a Picture Archiving and Communication System in Assistance-Publique-Hôpitaux de Paris, from 2007 to 2013. Dedicated software was used to analyse the presence or absence of at least 1 vertebral fracture (VF), and the radiodensity of the lumbar vertebrae was measured Hounsfield Units (HUs). A simulated T-score was calculated. RESULTS: Data were analysed from 152 268 patients [mean age (S.D.) = 73.2 (9.07) years]. Success rates for VF assessment and HUs measurements were 82 and 87%, respectively. The prevalence of VFs was 24.5% and increased with age. Areas under the receiver operating characteristic curves for the detection of VFs were 0.61 and 0.62 for the mean HUs of the lumbar vertebrae and the L1 HUs, respectively. In patients without VFs, HUs decreased with age, similarly in males and females. The prevalence of osteoporosis (sT-score ≤ -2.5) was 23.8% and 36.5% in patients without and with VFs, respectively. CONCLUSION: It is feasible on a large scale to screen for VFs and osteoporosis during opportunistic screening in patients 60 years or older having lumbar or abdominal CT.

Adult rheumatologic features, treatment and complications of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is a rare genetic phosphate disorder caused mainly by PHEX mutations. Unlike for children, knowledge of the disease's manifestations in adults is limited. Musculoskeletal symptoms are the main feature of the disease in young adults associated with a heavy burden on patients' life. They include fractures and pseudofractures, pain, joint stiffness, osteoarthritis, enthesopathies, and muscle weakness, eventually leading to impaired quality of life. Conventional treatment with phosphate supplements and vitamin D analogs is indicated in symptomatic patients. Appropriate rehabilitation is also a key to the management of the disease to improve physical function and decrease pain, stiffness, and fatigue. Regarding the incidence and consequences of musculoskeletal features in XLH, all patients should be assessed by a bone disease specialist and, if necessary, managed by a multidisciplinary team.

Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension.

OBJECTIVES: To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. METHODS: Adults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT). RESULTS: Subjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks. CONCLUSIONS: Adults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function. TRIAL REGISTRATION NUMBER: NCT02526160.

Contribution of imaging to the diagnosis and follow up of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is the most common form of inheritable rickets. The disease is caused principally by PHEX mutations leading to increased concentrations of circulating intact FGF23, hence renal phosphate wasting, hypophosphatemia, and decreased circulating levels of 1,25(OH)2 vitamin D. The chronic hypophosphatemia leads to rickets and osteomalacia through a combination of mechanisms, including a lack of endochondral ossification and impaired mineralization. Imaging has a major role in determining the diagnosis of rickets and its cause, detecting complications as early as possible, and helping in treatment monitoring.