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Aim: To describe the presenting features, bone characteristics and molecular genetics in a large monocentric cohort of children and young adults with idiopathic primary osteoporosis. Methods: Sixty-six patients (19 children, 47 adults; 28 males, 38 females; age at referral: 3.8 to 65 years) diagnosed with primary osteoporosis were included in this study; patients with features of osteogenesis imperfecta or other known syndromes associated with osteoporosis were excluded. For each patient, the following data were collected by retrospective chart review: family and personal history of fracture and osteoporosis, mineral homeostasis parameters and markers of bone formation and resorption, bone mineral density (BMD) of the lumbar spine (LS-BMD), the total body less head (TB-BMD), and total hip levels (TH-BMD) measured by DXA. As part of the initial assessment process, a bone fragility gene panel sequencing was performed in all of these patients. Results: There was a higher predominance of males in the children (63%) and of females in the adults (66%) (p = 0.030). Compared to the adults, the children had a significantly lower frequency of vertebral fractures (26 vs 57%, p = 0.022) and a higher frequency of peripheral fractures (84 vs 53%; p = 0.019). Bone fragility gene panel sequencing allowed the identification of the heterozygous pathogenic variant in 27% of patients (most frequently in LRP5, WNT1 and COL1A1 or 2 genes) and the heterozygous p.(Val667Met) LRP5 variant in 11% of them. The frequency of pathogenic variants tended to be higher in the children compared to the adults without reaching statistical significance (42 vs 19%; p = 0.053). The frequency of the p.(Val667Met) LRP5 variant was similar in children and adults. No significant differences were found regarding the various clinical, biological and radiological characteristics of the patients according to genotype. Conclusion: In this study, we reported the presenting features and bone characteristics in a large cohort of children and young adults with idiopathic primary osteoporosis. Bone fragility gene panel sequencing allowed the identification of genetic variants in a significant proportion of these patients. Molecular diagnosis in these patients is important in order to be able to offer genetic counselling and organise patient management.

Purpose: The occurrence of multiple vertebral fractures was reported after denosumab discontinuation. The use of bisphosphonates following denosumab has been suggested to prevent this bone loss. The aim of our observational trial was to evaluate the ability of risedronate to prevent the bone loss related to denosumab discontinuation in post-menopausal osteoporosis. Methods: Eighteen female patients, aged 69.8 years (56–79), were followed. All patients were prescribed 35 mg of risedronate per week for 3 months, starting when the next denosumab injection would have been administered. We measured BMD at denosumab initiation (T0), denosumab withdrawal (T1), and nine months after the discontinuation of risedronate (1 year post-denosumab: T2). Results: 1 year after denosumab discontinuation, the mean bone loss at the spine was – 4.6 ± 5.2% for the total population, −0.3 ± 2.3% in patients with prior exposure to bisphosphonates, −6.3 ± 5.7% in patients with prior exposure to teriparatide, and − 7.6 ± 3.5% in naïve patients. Spine BMD loss after the risedronate bridging therapy (T2 vs. T1) was significantly lower in patients who experienced prior exposure to bisphosphonates, when compared to naïve patients (p = .0190) and to patients with prior teriparatide exposure (p = .0176). 1 year after denosumab discontinuation, the mean densitometric loss at the hip was −1.8 ± 3.4% in the total cohort, −0.6 ± 1.8% in the patients previously treated with bisphosphonates, −1.5 ± 4.7% in the patients previously treated with teriparatide, and − 4.2 ± 0.6 in naïve patients. The mean densitometric loss during the off-denosumab period was lower in patients with previous bisphosphonate exposure than in naïve patients (p = .043) and in patients with previous exposure to teriparatide (p = .05). Conclusions: Three months of risedronate treatment does not prevent bone loss in patients who have not been treated with bisphosphonates before denosumab.