Sheila Shepherd

MRI-based abnormalities in young adults at risk of adverse bone health due to childhood-onset metabolic & endocrine conditions

Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro‐architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism.

A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis

Abstract Background: We aimed to describe the longitudinal changes in bone mineral content and influencing factors, in children with cystic fibrosis (CF). Methods: One hundred children (50 females) had dual X-ray absorptiometry (DXA) performed. Of these, 48 and 24 children had two to three scans, respectively over 10 years of follow-up. DXA data were expressed as lumbar spine bone mineral content standard deviation score (LSBMCSDS) adjusted for age, gender, ethnicity and bone area. Markers of disease, anthropometry and bone biochemistry were collected retrospectively. Results: Baseline LSBMCSDS was >0.5 SDS in 13% children, between −0.5; 0.5 SDS, in 50% and ≤−0.5 in the remainder. Seventy-eight percent of the children who had baseline LSBMCSDS >−0.5, and 35% of the children with poor baseline (LSBMCSDS<−0.5), showed decreasing values in subsequent assessments. However, mean LS BMC SDS did not show a significant decline in subsequent assessments (−0.51; −0.64; −0.56; p=0.178). Lower forced expiratory volume in 1 s percent (FEV1%) low body mass index standard deviation scores (BMI SDS) and vitamin D were associated with reduction in BMC. Conclusions: Bone mineral content as assessed by DXA is sub-optimal and decreases with time in most children with CF and this study has highlighted parameters that can be addressed to improve bone health.

An Unbalanced Rearrangement of Chromosomes 4:20 is Associated with Childhood Osteoporosis and Reduced Caspase-3 Levels.

The purpose of this study was to investigate the association of a chromosome 4:20 imbalance with osteoporosis in three related children. Bone biochemistry, bone turnover markers, and dual-energy X-ray absorptiometry (DXA) scanning were performed in all three cases and bone biopsy and histomorphometry in one. The chromosome imbalance was delineated by array comparative genomic hybridization (aCGH) and analyzed for candidate genes. A potential candidate gene within the deleted region is caspase-3, previously linked to low bone mineral density (BMD) in heterozygous mice thus caspase-3 activity was measured in cases and controls. Routine bone biochemistry and markers of bone turnover did not reveal any abnormality. DXA showed reduced total and lumbar spine bone mineral content. aCGH showed an 8 megabase (Mb) deletion of terminal chromosome 4q incorporating a region previously linked to low BMD and a 15 Mb duplication of terminal chromosome 20p. Bone biopsy showed a high bone turnover state, trabecularisation of cortical bone and numerous small osteoclasts coupled with normal bone formation. Basal serum caspase-3 activity was lower in cases compared with controls. We conclude that the early-onset osteoporosis with low basal levels of caspase-3 and abnormal osteoclasts is a feature of this chromosomal translocation. Further investigation of the role of the deleted and duplicated genes and especially caspase-3 is required.

Effects of Recombinant Human Growth Hormone in Children with Crohn’s Disease on the Muscle-Bone Unit: A Preliminary Study

Background/Aims: There is limited information on the impact of recombinant human growth hormone (rhGH) on the muscle-bone unit in children with Crohn’s disease (CD). In this pilot study, we report on the effects of rhGH on bone formation, dual-energy X-ray absorptiometry (DXA) total body (TB) bone mineral density adjusted for height and lumbar spine (LS) bone mineral apparent density (BMAD), and body composition. Methods: Prospective study of 8 children with CD (6 male), aged 14.8 years (9.0–16.4), who received rhGH for 24 months. Serum procollagen type 1 N-terminal propeptide (P1NP) was measured at baseline and at 6 months. DXA was performed every 6 months. Results: Six months of rhGH led to improvement in P1NP SDS adjusted for bone age from –3.6 (–7.9 to –0.9) to –2.4 (–3.7 to 0.4) (p = 0.01). At baseline, reduction in LS-BMAD and TB lean mass SDS was observed being –1.2 (–3.6 to 0.8) (p = 0.01 vs. zero) and –0.8 (–2.4 to 3.0) (p = 0.11 vs. zero), respectively. No significant changes were seen in DXA bone and muscle parameters over the 24 months. Conclusion: Twenty-four months of therapy with rhGH in CD did not lead to an improvement in DXA BMD and lean mass, despite improvement in P1NP and linear growth.

Longitudinal changes in bone parameters in young girls with anorexia nervosa

BACKGROUND Anorexia nervosa (AN) during childhood and adolescence has been reported to adversely affect bone health, but few studies have investigated longitudinal changes. METHOD DXA-derived bone parameters and body composition were retrospectively assessed in 111 young girls with AN with a median age of 15.4 years (10.9, 19.8). In 68 (61%) vertebral fracture assessment (VFA) was performed and in 31 (28%), a follow-up DXA was performed. Correlations with growth, changes in body composition and effects of illness duration and menstruation were examined. Size adjusted DXA standard deviation scores were calculated for total body (TB) less head bone mineral content (TBLH-BMC) and lumbar spine bone mineral apparent density (LS-BMAD). RESULTS Mean (range) bone area (BA) for height centile was 27.1 (0-97), and mean lean mass for height centile was 28.8 (0-95) at baseline. Mean (range) LS BMAD was -1.0 (-2.6, 0.8) SDS at first and - 1.2 (-3.0, -0.2) at second DXA (p = 0.023). On follow up, lean mass for height increased from 27th centile (0, 75) to 40th centile (0, 70) (p = 0.006), and fat mass for height increased from 55 g/cm to 67 g/cm (11.3, 124.2) (p < 0.001). Duration of illness was the only negative predictor of LS BMAD (p < 0.0001). Change in height SDS was the only positive predictor of change in TBLH-BMC (r = 0.384, p = 0.037), and change in LS BMAD (r-0.934, p < 0.0001). Of 68 patients who had VFA, 4 (5.9%) had a mild vertebral fracture. CONCLUSION Bones are smaller and less dense in childhood/adolescent AN compared to healthy adolescents. Although there are significant gains in lean mass and fat mass, over time, BMAD SDS decreases slightly. Improvement in BMAD SDS is related to improvement in height SDS.