Bone Mineral Content and Density in Rett Syndrome and Their Contributing Factors

Abstract

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and assess how factors such as genotype, epilepsy, BMI and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy X-ray absorptiometry. Mean height standardised z-scores and confidence intervals for the bone outcomes were obtained from multiple regression models. The mean height z-score for the FN aBMD was low at −2.20, while the LS aBMD was −0.72. The TBBMC mean height z-score was −0.62, although once adjusted for BA and LTM the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168X and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relation between genotype, BMC and aBMD, is likely underpinned by the strong relation between LTM, mobility and bone outcome measures.

Clinical and biological progress over 50 years in Rett syndrome

“…172,173 Fracture risk was four times that of the general female population, and specifically increased in those with p.Arg168* and p.Arg270*mutations (see Fig 2). 173 Several Danish, 174,175 US 176,177 and further Australian studies 178,179 have also investigated which particular bone parameters were most adversely affected and their potential nutritional, 180 (e.g. Vitamin D status) environmental and genetic risk factors.…”

“…For example, right femoral neck areal bone mineral density was particularly impaired with increasing age and lack of mobility in comparison to other parameters. 178 A recent Danish study concluded that the comparatively reduced levels of biochemical bone markers in RTT signified a a low bone turnover state. 182 Nonrepresentative and small sample sizes, often without longitudinal collection, lack of childhood population bone parameter norms and accommodation for decreased stature and different analytical methods all make cross-study comparison difficult.…”

Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

“…However, in general, studies have reported conflicting associations of the effects of physical activity on bone turnover in different populations (37). Also, DXA studies of the association between bone mass and ambulant ability in RTT have shown diverging results (4,6,7,13,38).…”

“…Previously, dual-energy x-ray absorptiometry (DXA) studies have reported low bone mass in patients with RTT (4)(5)(6)(7)(8), and increased occurrence of low-energy fractures in these patients has also been shown (9). Patients with RTT are often growth retarded (10).…”

Low Bone Mineral Mass Is Associated With Decreased Bone Formation and Diet in Girls With Rett Syndrome

“…An observational study such as ours identifies factors associated with low bone mineral mass, but they may not be causally related. Small body size, deficits in lean body mass, anticonvulsant use, and nonambulatory status contribute to poor bone mineral status (3,24,29,30). Furthermore, the determination of BMD by dual energy x-ray absorptiometry should be made cautiously in individuals with short stature insofar as smaller, adequately mineralized bones may appear less dense by this method.…”