We found high prevalence of osteoporosis and abnormal glucose metabolism in subjects with LRP5 mutation(s). Further studies are needed to establish the role of LRP5 in glucose and lipid metabolism.

Previous studies have indicated that children with inflammatory bowel disease (IBD) may not achieve optimal bone mass. We evaluated the skeletal characteristics in children and adolescents with IBD. This cross-sectional cohort study comprised 80 IBD patients (median age 14.9 years, range 5-20) with a median disease duration of 3.4 years; 51 had ulcerative colitis, 26 Crohn disease, and 3 unspecified colitis. Eighty age- and gender-matched healthy subjects served as controls. Areal bone mineral density (aBMD), body composition, and vertebral fractures (VFs) were assessed by DXA. Bone age (BA) was determined for IBD patients. Findings were correlated with disease- and treatment-related parameters and biochemistry. IBD patients had lower BA-adjusted lumbar spine and whole-body aBMD (p < 0.001 for both) and whole-body BMC adjusted for height (p = 0.02) than controls. Lean mass and fat mass Z scores did not differ between the groups, but IBD patients had lower whole-body BMC relative to muscle mass (p = 0.006). Despite vitamin D supplementation in 48 %, vitamin D deficiency was common. In IBD cumulative weight-adjusted prednisolone dose >150 mg/kg for the preceding 3 years increased the risk for low whole-body aBMD (OR = 5.5, 95 % CI 1.3-23.3, p = 0.02). VFs were found in 11 % of patients and in 3 % of controls (p = 0.02). IBD in childhood was associated with low aBMD and reduced bone mass accrual relative to muscle mass; the risk for subclinical VFs may be increased. These observations warrant careful follow-up and active preventive measures.

Objective: Long-term health sequelae of childhood-onset acute lymphoblastic leukemia (ALL) remain largely unknown. Low bone mineral content (BMC) and bone mineral density (BMD) are recognized complications, but it is unknown whether these persist until adulthood. We evaluated skeletal characteristics and their association with ALL therapy in long-term male ALL survivors. Design: This cross-sectional cohort study included 49 long-term male ALL survivors and 55 agematched healthy males. Methods: BMD and compression fractures were assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for parameters of calcium homeostasis. Results: The ALL survivors (median age 29 years, range 25-38 years), assessed 10-38 years after ALL diagnosis, had lower lumbar spine (P!0.001), femoral neck (P!0.001), and whole-body (PZ0.017) BMD than expected based on normative values. When compared with the controls (median age 30 years, range 24-36 years), the ALL survivors had lower lumbar spine BMC (PZ0.014), lower whole-body BMC (P!0.001), and lower whole-body BMD (P!0.001), but the differences were partly explained by differences in height. Altogether, 20% of the ALL survivors had spinal compression fractures, but these were equally prevalent in the controls. Males diagnosed with ALL before age 5 years had significantly lower BMD values. Other recognized risk factors included untreated hypogonadism, vitamin D deficiency, hypophosphatemia, low IGF-binding protein-3, and low physical activity. Conclusions: At young adulthood, long-term male ALL survivors have significantly reduced BMC and BMD and a high prevalence of spinal compression fractures. Careful follow-up and active treatment of the recognized risk factors are warranted.

Severe JIA is associated with a significant risk of vertebral compression fractures. Associated factors include high disease activity, high BMI, and high recent GC exposure. Further studies are needed to establish optimal prevention and treatment guidelines.

High-dose therapy and hematopoietic stem cell transplantation (HSCT) have been shown to improve survival rates in high-risk neuroblastoma (HR-NBL), but may cause adverse effects on the growing skeleton. We studied skeletal health in a national cohort of long-term survivors of HR-NBL (n=21; age 16-30 years, median 22 years) and in 20 healthy age- and sex-matched controls. In addition to clinical evaluation and measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry, we performed spinal magnetic resonance imaging. Skeletal complications were categorized according to Common Terminology Criteria for Adverse Events (CTCAE). Altogether, 18/21 survivors presented with at least one skeletal adverse event according to CTCAE, the most common skeletal complications being short stature (n=14) and osteopenia (n=13). Altogether, 38% of the subjects had a severe complication (CTCAE score ⩾3) including bilateral slipped capital femoral epiphyseolysis in 3/21. Fracture rate was not increased. In spinal MRI, no vertebral fractures were found and degenerative intervertebral disc changes were equally prevalent in survivors and controls. BMD was lower in survivors than controls, but differences became non-significant when adjusted for bone size. In conclusion, skeletal late complications are common and can significantly impair the quality of life in young adult survivors of HR-NBL treated with high-dose protocols and HSCT.