[Metabolic bone diseases : what's new in 2023]. / Maladies osseuses : ce qui a changé en 2023.

The sequential effects of romosozumab and denosumab in osteoporosis are shown in real-life, while the mechanisms of post-denosumab rebound are reviewed extensively. A network meta-analysis confirms the superiority of anabolics vs anti-resorptives on fracture reduction, while the latter shown a reduction of mortality in a large population-based study. Fracture risk prediction by FRAXPlus is improved. New meta-analyses confirm the benefits of Vitamin D on fractures and falls. Finally, multiples trials with new molecules for the treatment of rare bone diseases, including osteogenesis imperfecta, fibrous dysplasia and hypoparathyroidism, shown promising results.

Dans l'ostéoporose, les effets séquentiels du romosozumab et du dénosumab se précisent et les mécanismes du rebond à l'arrêt de ce dernier font l'objet d'une revue détaillée. Une méta-analyse en réseau confirme la supériorité des traitements anaboliques sur les antirésorbtifs, alors que l'effet de ces derniers sur la réduction de la mortalité est démontré dans une large étude populationnelle. La prédiction du risque fracturaire est améliorée par l'outil FRAXPlus. De nouvelles méta-analyses des bénéfices de la vitamine D sur le risque de fractures et de chutes sont également disponibles. Enfin, de nombreuses études encourageantes sur l'efficacité de nouveaux traitements dans de multiples maladies osseuse rares, telles l'ostéogenèse imparfaite, la dysplasie fibreuse et l'hypoparathyroïdie, ont été publiées.

[Rare causes of Hypophosphatemia: diagnostic approach]. / Hypophosphatémies de causes rares : approche diagnostique.

Hypophosphatemia is common and may be overlooked due to its asymptomatic nature or non-specific symptoms. Two main mechanisms are at its origin: a shift towards the intracellular sector and an increase in urinary phosphate excretion. A measurement of the urinary phosphate reabsorption threshold allows a diagnostic orientation. Alongside common forms of parathyroid hormone-dependent hypophosphatemia, one should not ignore rare FGF23-mediated forms, in particular X-linked hypophosphatemic rickets. The treatment, above all etiological, also includes the administration of phosphate and, in the event of an excess of FGF23, supplementation with calcitriol. In cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets, the use of burosumab, an anti-FGF23 antibody, must be considered.

L'hypophosphatémie est fréquente. Pourtant, elle peut parfois être méconnue de par son caractère asymptomatique ou ses symptômes non spécifiques. Deux grands mécanismes sont à son origine : un shift vers le secteur intracellulaire et une augmentation de l'excrétion urinaire de phosphate. Une mesure du seuil de réabsorption urinaire de phosphate permet une orientation diagnostique. À côté de formes communes d'hypophosphatémies parathormone-dépendantes, il ne faut pas méconnaître des formes rares FGF23 médiées, en particulier le rachitisme hypophosphatémique lié à l'X. Le traitement, avant tout étiologique comporte aussi l'administration de phosphate et lors d'un excès de FGF23, une supplémentation en calcitriol. En cas d'ostéomalacie oncogénique et de rachitisme hypophosphatémique lié à l'X, l'emploi de burosumab, anticorps anti-FGF23, doit être considéré.

Time for Revival of Bone Biopsy with Histomorphometric Analysis in Chronic Kidney Disease (CKD): Moving from Skepticism to Pragmatism.

Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.

[Osteoporosis in patients with chronic renal failure : evaluation and management ? Role of bone biopsy]. / Ostéoporose chez l'insuffisant rénal : quelle évaluation et quel traitement ? Place de la biopsie osseuse.

The management of osteoporosis in patients with mild to moderate chronic kidney disease (CKD) can be established as in general population. In severe or terminal CKD, bone densitometry is indicated. Bone-specific alkaline phosphatase is considered a useful marker for distinguishing among the histologic types of renal osteodystrophy. In ambiguous cases, bone biopsy together with quantitative histomorphometry will be necessary. As far as the treatment is concerned, the bisphosphonates, which had been avoided due to their renal excretion as well as the official warnings against using them in case of renal clearance lower than 30 ml/min, seem to be effective even in advanced stages of renal disease. There are limited data, though, regarding the management of osteoporosis in terminal stages of CKD.

La prise en charge des patients en insuffisance rénale légère à modérée peut être calquée sur celle de la population générale. En cas d'insuffisance rénale sévère ou terminale, la densitométrie osseuse reste indiquée. Le type d'ostéodystrophie rénale sera présumé à partir du niveau de phosphatase alcaline osseuse. Dans les cas équivoques, une biopsie osseuse avec histomorphométrie quantitative sera nécessaire. Quant au traitement, les bisphosphonates, longtemps mis à l'écart vu leur élimination rénale et la contre-indication de principe existant pour la plupart d'entre eux pour des niveaux de clairance inférieure à 30 ml/min, sont efficaces même à des stades avancés de l'insuffisance rénale. La prise en charge de l'ostéoporose chez l'insuffisant rénal terminal reste encore un domaine avec des données limitées.

Giant osteoclasts in patients under bisphosphonates.

BACKGROUND: Bisphosphonates have been widely used for treatment of high bone resorption states. It lowers bone turnover by inhibiting osteoclasts bone resorption with various mechanisms of actions: inhibition of osteoclast formation and attachment to the bone surface, induction of metabolic injury, alteration of vesicle trafficking and induction of osteoclast apoptosis. Bone biopsies studies from patients under bisphosphonates have shown that some resorption parameters are decreased as expected but the number of osteoclasts seems not to be necessarily decreased. The description of osteoclasts morphology from patients treated with bisphosphonates has rarely been reported in the literature. CASE PRESENTATION: We describe in this paper two patients treated with bisphosphonates from whom iliac crest bone biopsies have shown large, multinucleated and apoptotic osteoclasts that were not associated with bone resorption activities. The characteristics of these osteoclasts are described and the literature reviewed. CONCLUSION: The appropriate recognition of these giant osteoclasts in bone tissues from patients treated with bisphosphonates is of primary importance for bone pathologists and should not be interpreted as signs of increased bone resorption as seen in hyperparathyroidism, bone cancer or Paget's disease of bone.

Outcome and risk factors for late-onset complications 24 months beyond allogeneic hematopoietic stem cell transplantation.

OBJECTIVES: The aim of this retrospective study was to assess the incidence of late complications occurring ≥2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T-cell depletion strategy. METHODS: Between 1984 and 2004, 142 patients were eligible for the study. Total body irradiation (TBI) was carried out in 85% of the patients and T-cell depletion in 84%. RESULTS: Non-relapse mortality (NRM) was 3% (95% CI 0-11) at 10 years, and serious late events affected a substantial number of patients. The cumulative incidence (CI) of chronic graft-versus-host disease (cGvHD) was 30% (95% CI 23-40), and that of infectious complications was 17% (95% CI 11-23). Multivariate analysis showed a higher risk for late complications in patients with cGvHD (HR 1.9, 95% CI 1.2-3.2, P=0.011) and patients receiving methylprednisolone during conditioning (HR 1.9, 95% CI 1.1-3.3, P=0.019 1), patients with cGvHD also having a higher risk for NRM (HR 13.2, 95% CI 1.2-143, P=0.03), as well as those receiving steroids for >3 months (HR 40.3, 95% CI 2.3-718, P=0.02) and those receiving antithymocyte globulin (HR 9.6, 95% CI 0.8-68, P=0.024). CONCLUSIONS: A significant proportion of long-term survivors of HSCT had late complications. cGvHD remained an important risk factor for late complications despite T-cell depletion resulting in immunosuppression and infectious complications.

Increase in bone mineral density after successful parathyroidectomy for tertiary hyperparathyroidism after renal transplantation.

BACKGROUND: Few studies have reported changes of bone mineral density (BMD) after parathyroidectomy in patients with persistent hyperparathyroidism after renal transplantation (3 HPT). PATIENTS AND METHODS: We retrospectively analyzed 14 patients who underwent successful parathyroidectomy for 3 HPT and who had available BMD data before and after parathyroidectomy. RESULTS: Median follow-up time was 26 months (IQR: 16.8-40.2). Serum calcium levels decreased significantly after parathyroidectomy (2.32 +/- 0.09 versus 2.66 +/- 0.16 mmol/l; p < 0.01), as did PTH levels (5.1 +/- 3.0 versus 27.8 +/- 23.7 pmol/l; p < 0.01). Nine patients (64%) had a steroid-free immunosuppression at follow-up. Mean increase in BMD was 9.5 +/- 8.0% for the spine and 9.5 +/- 7.9% for the hip (p < 0.01 for both sites). Patients with osteoporosis (T-score

Cervical Paget disease of bone with spinal cord compression due to atlanto-axial instability: a case report and review of the literature.

STUDY DESIGN: Case report. OBJECTIVE: To describe a case of polyostotic Paget disease of bone (PDB), with axis, lumbar, and calcaneum involvement. SUMMARY OF BACKGROUND DATA: PDB can involve cervical spine. This can lead to cervical cord compression and cervical myelopathy. A cranio-cervical instability has been rarely described in patients with PDB. METHODS AND RESULTS: We report about the case of a 65-year-old women presenting with a polyostotic PDB, with axis, lumbar, and calcaneum involvement. The C2 vertebral lesion was associated with an atlantoaxial instability due to a pathologic odontoid fracture and was responsible for progressive spinal cervical cord compression. The patient was operated on by a posterior approach allowing spinal cord decompression, C0-C4 stabilization, and pathologic tissue sampling. Pathologic examination confirmed the diagnosis of Paget disease. The bisphosphonate therapy was started. Radiologic follow-up showed a good cranio-cervical alignement and an unchanged axis lesion. CONCLUSION: Even if the treatment of pagetic spinal stenosis symptoms should start with medical therapy, surgery can sometimes be performed earlier to treat neural compression due to spinal instability, with favorable outcome.

[Anorexia nervosa and its consequences on bone: a therapeutic challenge]. / Anorexie mentate et ses conséquences osseuses: une prise en charge difficile.

It has been estimated that osteoporosis is present in 20 to 50% of women with anorexia nervosa, with an increased fracture risk particularly at non vertebral sites. Thus, bone loss is a major clinical concern in anorexia nervosa patients, justifying systematic evaluation. However, evidence-based therapeutic options are limited.

Survival after parathyroidectomy in patients with end-stage renal disease and severe hyperparathyroidism.

BACKGROUND: Patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism (SHPT) are at high risk of mortality. Whether an increased risk of death persists after a parathyroidectomy (PTX) is not clearly established. SUBJECTS AND METHODS: The survival of 40 patients with ESRD and SHPT who underwent PTX was compared with that of 664 ESRD patients. RESULTS: From first dialysis, a lower mortality rate was found in the group of patients who underwent PTX than in the nonoperated ESRD group (hazard ratio: 0.23; 95% CI: 0.14-0.37). The patients who underwent PTX were younger, had a longer time on dialysis, and had a higher prevalence of kidney transplantation. The mean number of comorbidities was lower (Charlson score 4.2 +/- 2.1 versus 6.4 +/- 2.9, p < 0.001). Then, we randomly selected two matched controls for each PTX case (80 controls, 40 PTX) who had at least an equivalent mean duration of dialysis between the first dialysis and PTX of the PTX group. In a univariate model, there was a trend for PTX being associated with prolonged survival. The mortality was higher both among those at an advanced age and those with a high Charlson score. Adjustments for these covariates made the effect of PTX no more significant. CONCLUSIONS: The risk of death of patients with severe SHPT leading to PTX differed from that of nonoperated subjects. The apparent differences in survival may be related to the number and severity of associated comorbidities. ESRD patients who undergo PTX may represent a subset of healthier subjects.

Primary hyperparathyroidism: can parathyroid carcinoma be anticipated on clinical and biochemical grounds? Report of nine cases and review of the literature.

BACKGROUND: Parathyroid carcinoma (PC) mimics benign primary hyperparathyroidism (PHP), but the diagnosis of PC is seldom available at the time of the first operation. Because PC is plagued by recurrences usually beyond cure, one may wonder whether some of these could be prevented by more extensive resections initially, i.e., if the diagnosis of PC were available at that time. METHODS: Over a 25-year period, 311 consecutive patients with PHP underwent operation in our department: 302 had benign disease (adenomas or hyperplasias), and 9 had PC. Several clinical parameters, serum calcium and parathyroid hormone (PTH) levels, and the weight of the parathyroid tumor removed were compared in both groups. Receiver operating characteristic curves and logistical regression analyses were used to distinguish PC from benign PHP. RESULTS: Eight of 9 patients with PC had symptoms, versus 238 (79%) of 302 with benign PHP (not significant). In the PC subgroup, serum calcium and PTH levels and the tumor weights of the parathyroid glands removed were significantly higher than in the benign PHP cohort, even if these three parameters were regularly flawed by low positive predictive values (14%, 20%, and 15%, respectively). CONCLUSIONS: Serum calcium, PTH levels, and tumor weights were significantly greater in the PC subgroup, even if not invariably in a discriminatory way. However, when PTH is <4 times the upper limit of normal and tumor weight is <1.9 g, the probability of PC is nil.

Giant bone islands: a case with 31 years of follow-up.

A dense bone lesion raises immediate concern about the possibility of a primary or secondary tumor. Stability of the image over time is a strong argument against a malignancy. Benign solitary bone islands are usually believed to remain stable over time, with no tendency toward growth. We report a case in a patient with 31 years of follow-up, during which marked growth of the island was documented. The bone scan was normal, and histology established the diagnosis of benign bone island. In a patient with an enlarging sclerotic lesion, typical radiographic features and absence of radionuclide uptake are strong arguments in favor of a bone island.