Michel Laroche

Stopping treatment for osteoporosis with denosumab (Dmab) leads to a major and rapid loss in bone mineral density (BMD) and a risk of vertebral fracture. Subsequent treatment with bisphosphonate (Bp) does not completely prevent this bone loss. We carried out a prospective pilot study to find out whether the gradual dose reduction with denosumab could prevent this bone loss. We proposed a therapeutic protocol consisting in reducing the doses of Dmab to women treated with Dmab for postmenopausal osteoporosis. Six months after the last dose of Dmab 60 mg, the subsequent injection was performed with a reduced dose of 30 mg, and the month‐12 injection was a 15‐mg injection. BMD and serum C‐terminal telopeptide of type I collagen (CTX) were measured at the start of treatment with Dmab (T0), at the last dose with 60 mg (T1), and at 6 months (T2) and 12 months (T3) after the last 15 mg Dmab injection. We included 13 patients aged 68.7 ± 3 years, and treated with Dmab for 45.2 ± 5 months. At the lumbar spine, 39% of the initial gain in BMD was preserved 1 year after the last dose (15 mg). Conversely, at the hip, the bone loss at the end of the treatment reduction protocol was equivalent to the initial gain. The mean CTX level was 166 ± 152 pg/mL 6 months after the last dose (T2; 15 mg), and 549 ± 425 pg/mL 12 months after the last dose (T3; 15 mg). One patient presented two vertebral fractures, 8 months after the last dose of Dmab (15 mg). Gradual dose reduction of denosumab (30 mg then 15 mg) does not prevent bone loss in the hip and partially maintains the initial gain at the spine. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

10% of rheumatoid arthritis (RA) cases are associated to so-called secondary Sjögren's syndrome (SS). These RA cases have higher DAS, fewer remissions. Is this linked to a poor response to DMARDs (disease-modifying anti-rheumatic drugs)? No study has addressed this question to date. Does the association between secondary Sjögren's syndrome (SS) and rheumatoid arthritis (RA) affect the therapeutic response to DMARDs and long-term prognosis? We conducted a retrospective case–control study: 39 RA associated with SS was (anti-SSA antibodies and/or Chisolm stage III or IV) were compared to 39 isolated cases of erosive RA matched by age, duration of progression and gender. The DAS CRP was higher in the RA + SS group in patients with disease progression of 16 years: 2.6 (1.5–4.5) compared to the RA group: 1.6 (1.3–2.8) (p = 0.0001) while fewer patients were in remission: 61 vs. 92% (p = 0.002). A higher number of B DMARDs have been prescribed: RA + SS = 3.04 (1–7); RA = 1.7 (1–5) (p = 0.004). Anti-TNFs are less effective when RA is associated with SS: 30 vs. 70%. Conversely, Rituximab is more effective when RA is associated with SS: 80 vs. 30%. Erosive RA-related SS exacerbates the clinical course of the condition: higher DAS, fewer remissions. This is linked to reduced treatment efficacy: higher number of DMARDs prescribed, reduced efficacy of anti-TNF drugs. RA-related SS could modify sensitivity to biotherapies: lower percentage of remissions and resistance to anti-TNF drugs.

Treatment with asfotase alfa has transformed the prognosis of hypophosphatasia in children and improves the bone and muscle signs in adults. The doses used in adults are the same as in children, whereas bone remodeling is different between them. We report on the cases of two patients treated with 1 mg/kg/day of asfotase alfa who developed spinal cord compression from spinal ossifications during treatment. The first patient, 50 years old, presented after 2 years of treatment with quadraparesis secondary to an increase in ossifications of the cervical vertebral ligaments. The neurological damage was resolved after laminectomy, and the patient was then treated for 18 months with doses of 80 mg per week, without recurrence of the bone and muscle signs. The second patient, 26 years old, 78 kg, developed pain and cervical stiffness with pyramidal tract irritation secondary to ossifications of the vertebral ligaments. This improved with a reduction of doses to 80 mg/week, which then, after 6 months of follow‐up, enabled maintained improvement of the bone and muscle pain that was initially obtained. To our knowledge, these are the first reported cases of increased spinal ligamentous ossifications with neurological complications. Biological monitoring in adults does not seem to enable asfotase alfa doses to be adjusted. The levels of serum alkaline phosphatase (ALP) while on the recommended treatment of 1 mg/kg/day are significantly supraphysiological (5000 to 20,000 IU) and the assays of pyrophosphate and pyridoxal phosphate are not correlated with clinical efficacy. In both of our patients, the treatment with 80 mg of asfotase alfa per week, which was proposed after the occurrence of spinal complications, seemed as effective, after a follow‐up of 18 months and 6 months, as the initial treatment for improving the bone and muscle signs, and could be provided as “attack” doses after healing of the pseudoarthroses. © 2021 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.