Phillip Wong

Musculoskeletal and Endocrine Health in Adults With Cerebral Palsy: New Opportunities for Intervention

CONTEXTnCerebral palsy (CP) increases fracture risk through diminished ambulation, nutritional deficiencies, and anticonvulsant medication use. Studies examining bone mineral density (BMD) in adults with CP are limited.nnnOBJECTIVEnTo examine the relationship between body composition, BMD, and fractures in adults with CP. The effect of functional, nutritional, and endocrine factors on BMD and body composition is also explored.nnnDESIGNnRetrospective cross-sectional study.nnnSETTING AND PARTICIPANTSnForty-five adults with CP (mean age, 28.3 ± 11.0 years) who had dual-energy x-ray absorptiometry imaging at a single tertiary hospital between 2005 and 2015.nnnRESULTSnSeventeen (38%) had a past history of fragility fracture; 43% had a Z-score of ≤ -2.0 at the lumbar spine (LS) and 41% at the femoral neck (FN). In nonambulatory patients, every one unit decrease in FN Z-score increased the risk of fracture 3.2-fold (95% confidence interval, 1.07-9.70; P = .044). Stepwise linear regression revealed that the Gross Motor Function Classification System was the best predictor of LS Z-score (R(2) = 0.550; β = -0.582; P = .002) and FN Z-score (R(2) = 0.428; β = -0.494; P = .004); 35.7% of the variance in BMD was accounted for by lean tissue mass. Hypogonadism, present in 20% of patients, was associated with reduced lean tissue mass and reduced LS BMD. Lean tissue mass positively correlated with BMD in eugonadal patients, but not in hypogonadal patients.nnnCONCLUSIONSnLow BMD and fractures are common in adults with CP. This is the first study to document hypogonadism in adults with CP with detrimental changes in body composition and BMD.

Bone Disease in Thalassemia: A Molecular and Clinical Overview

Thalassemia bone disease is a common and severe complication of thalassemia-an inherited blood disorder due to mutations in the α or β hemoglobin gene. In its more severe form, severe anemia is present, and treatment with frequent red blood cell transfusion is necessary. Because the body has limited capacity to excrete iron, concomitant iron chelation is required to prevent the complications of iron overload. The effects of chronic anemia and iron overload can lead to multiple end-organ complications such as cardiomyopathy, increased risks of blood-borne diseases, and liver, pituitary, and bone disease. However, our understanding of thalassemia bone disease is incomplete and is composed of a complex piecemeal of risk factors that include genetic factors, hormonal deficiency, marrow expansion, skeletal dysmorphism, iron toxicity, chelators, and increased bone turnover. The high prevalence of bone disease in transfusion-dependent thalassemia is seen in both younger and older patients as life expectancy continues to improve. Indeed, hypogonadism and GH deficiency contribute to a failure to achieve peak bone mass in this group. The contribution of kidney dysfunction to bone disease in thalassemia is a new and significant complication. This coincides with studies confirming an increase in kidney stones and associated accelerated bone loss in the thalassemia cohort. However, multiple factors are also associated with reduced bone mineral density and include marrow expansion, iron toxicity, iron chelators, increased bone turnover, GH deficiency, and hypogonadism. Thalassemia bone disease is a composite of not only multiple hormonal deficiencies but also multiorgan diseases. This review will address the molecular mechanisms and clinical risk factors associated with thalassemia bone disease and the clinical implications for monitoring and treating this disorder.

Delay in estrogen commencement is associated with lower bone mineral density in Turner syndrome

Abstract Objective: Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures. We investigated the prevalence and risk factors for low bone density and fractures in a TS cohort. Methods: We included 76 TS patients (median age 28.5 years) attending a tertiary hospital between 1998 and 2015 who underwent dual-energy X-ray absorptiometry. Spine and femoral neck (FN) areal bone mineral density (aBMD) were compared with those of a control group. To adjust for smaller bone size, bone mineral apparent density (BMAD) was calculated. Results: Primary amenorrhea was common (83%) in the TS cohort; the median age of pubertal induction was 15 years (range 11–30 years), and non-continuous estrogen therapy (ET) recorded in 40%. Almost one-third of TS patients reported fractures. TS patients had lower median spinal aBMD (1.026u2009g/cm2 vs. 1.221u2009g/cm2) and BMAD (0.156u2009g/cm3 vs. 0.161u2009g/cm3) than controls, and lower median FN aBMD (0.850u2009g/cm2 vs. 1.026u2009g/cm2) (all pu2009<u20090.01). More women with TS had spinal Z-scoreu2009<u2009−2.0 compared to controls (26.0% vs. 3.6%, pu2009=u20090.001). Spine and FN aBMD, BMAD and Z-scores were inversely associated with age commencing ET or years of estrogen deficiency. Conclusions: Delay in ET commencement was an independent risk factor for the lower bone density observed in women with TS. Early pubertal induction and ET compliance are important targets to optimize aBMD.

Fractures in spina bifida from childhood to young adulthood

SummaryThis study assessed the prevalence and types of fractures in spina bifida and examined risk factors for fracture. Fracture prevalence was highest in childhood and reduced in adolescence and young adulthood. The importance of maintaining mobility is highlighted by the increased risk of fracture in those who are non-ambulatory.IntroductionThe aims of this study are to study the prevalence and types of fractures according to age group in spina bifida and examine risk factors associated with fracture.MethodsThis is a retrospective cohort study of 146 individuals with spina bifida aged 2xa0years or older who attended the paediatric or adult spina bifida multidisciplinary clinic at a single tertiary hospital.ResultsMedian age at which first fracture occurred was 7xa0years (interquartile range 4–13xa0years). Fracture rates in children (ages 2–10), adolescents (ages 11–18) and adults (agexa0>xa018) were 10.9/1000 (95xa0% confidence interval 5.9–18.3), 5.4/1000 (95xa0% CI 1.5–13.8) and 2.9/1000 (95xa0% CI 0.6–8.1) patient years respectively. Childhood fractures predominantly involved the distal femur and femoral shaft; these fractures were rarely seen in adulthood. Non-ambulatory status was associated with a 9.8 times higher risk of fracture compared with ambulatory patients (odds ratio 9.8, pxa0=xa00.016, 95xa0% CI 1.5–63.0). Relative risk of re-fracture was 3.1 (95xa0% CI 1.4–6.8). Urological intervention with intestinal segments was associated with renal calculi (pxa0=xa00.037) but neither was associated with fracture.ConclusionsThe risk of fracture is lower in adults compared with children with spina bifida. The predominant childhood fracture affects the distal femur, and immobility is the most significant risk factor for fracture. Clinical factors contributing to fracture risk need to be elucidated to enable selection of patients who require investigation and treatment of osteoporosis.

Sex hormone–binding globulin is a biomarker associated with nonvertebral fracture in men on dialysis therapy

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.

Serum phosphorus levels and fracture following renal transplantation

Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders.1 Low serum phosphorus levels occur post‐transplantation; however, its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre.

A Cross-Sectional and Longitudinal Analysis of Trabecular Bone Score in Adults With Turner Syndrome

ContextnTurner syndrome (TS) is associated with short stature, gonadal failure, and fractures. Spinal trabecular bone score (TBS) is a novel bone imaging modality that has not been evaluated in TS.nnnObjectivenTo evaluate TBS in TS and its association with bone mineral density (BMD), prevalent fracture, and risk factors.nnnDesign and SettingnLongitudinal study of TS from a single tertiary hospital between 2006 and 2017.nnnPatients or Other ParticipantsnFifty-eight subjects with TS aged 20 to 49 years who underwent dual-energy X-ray absorptiometry (DXA).nnnMain Outcome MeasuresnTBS, DXA parameters, and prevalent fractures were investigated.nnnResultsnNormal, partially degraded, and degraded TBSs were observed in 39 (67%), 15 (26%), and four (7%) subjects, respectively. High rates of prescribed estrogen replacement therapy (ERT) with stable TBS and BMD were observed during follow-up. TBS was positively correlated with spine and femoral neck (FN) BMD and Z-scores (all P < 0.05) and negatively correlated with age (-0.004 per year; P = 0.014) and delay in ERT initiation in women with primary amenorrhea (-0.010 per year; P < 0.001). Fractures were present in 17 (31%) subjects. Low TBS had a significantly higher area under the receiver operator curve for predicting prevalent fracture than low bone mass at either the spine or FN (P < 0.05). Subjects with no history of fracture were more likely to have a normal TBS (P = 0.023).nnnConclusionsnBMD and TBS can be preserved with early initiation and continued use of ERT. TBS may provide additional fracture risk prediction to standard DXA parameters in TS and needs to be validated in larger prospective studies.

Recurrent vertebral fractures in a young adult: a closer look at bone health in type 1 diabetes mellitus

Summary The association between type 1 diabetes mellitus (T1DM) and bone health has garnered interest over the years. Fracture risk is known to be increased in individuals with T1DM, although bone health assessment is not often performed in the clinical setting. We describe the case of a 21-year-old male with longstanding T1DM with multilevel vertebral fractures on imaging, after presenting with acute back pain without apparent trauma. Dual-energy X-ray absorptiometry (DXA) revealed significantly reduced bone mineral density at the lumbar spine and femoral neck. Extensive investigations for other secondary or genetic causes of osteoporosis were unremarkable, apart from moderate vitamin D deficiency. High-resolution peripheral quantitative computed tomography and bone biospy revealed significant alterations of trabecular bone microarchitecture. It later transpired that the patient had sustained vertebral fractures secondary to unrecognised nocturnal hypoglycaemic seizures. Intravenous zoledronic acid was administered for secondary fracture prevention. Despite anti-resorptive therapy, the patient sustained a new vertebral fracture after experiencing another hypoglycaemic seizure in his sleep. Bone health in T1DM is complex and not well understood. There are significant challenges in the assessment and management of osteoporosis in T1DM, particularly in young adults, where fracture prediction tools have not been validated. Clinicians should be aware of hypoglycaemia as a significant risk factor for fracture in patients with T1DM. Learning points: Type 1 diabetes mellitus (T1DM) is a secondary cause of osteoporosis, characterised by reduced bone mass and disturbed bone microarchitecture. Hypoglycaemic seizures generate sufficient compression forces along the thoracic column and can cause fractures in individuals with compromised bone quality. Unrecognised hypoglycaemic seizures should be considered in patients with T1DM presenting with fractures without a history of trauma. Patients with T1DM have increased fracture risk and risk factors should be addressed. Evaluation of bone microarchitecture may provide further insights into mechanisms of fracture in T1DM. Further research is needed to guide the optimal screening and management of bone health in patients with T1DM.

Increased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease

Both Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) are independently associated with reduced bone mineral density (BMD) and increased fracture risk. Whilst poorer glycaemic control and increased microvascular complications have been described, the literature examining bone health and fractures in adults with concomitant T1DM and CD (T1DM + CD) is limited.

Trabecular bone score in adults with cerebral palsy

CONTEXTnBone fragility in cerebral palsy (CP) is secondary to a complex interplay of functional, hormonal, and nutritional factors that affect bone remodelling. A greater understanding of bone microarchitectural changes seen in CP should assist therapeutic decision making.nnnOBJECTIVEnTo examine the relationship between trabecular bone score (TBS), BMD and fractures in adults with CP; the influence of clinical factors and body composition on bone microarchitecture were explored.nnnDESIGNnRetrospective cross-sectional study.nnnSETTING AND PARTICIPANTSn43 adults (25 male) with CP of median age 25u202fyears (interquartile range 21.4-33.9) who had evaluable dual-energy X-ray absorptiometry imaging of the lumbar spine from a single tertiary hospital between 2005-March 2018.nnnRESULTSn24/43 (55.8%) of patients had TBS values indicating intermediate or high risk of fracture (<1.31). TBS correlated with areal BMD at the lumbar spine, femoral neck and total body. TBS was significantly associated with arm and leg lean mass, with adjustment for age, gender and height (adjusted R2u202f=u202f0.18, pu202f=u202f0.042 for arm lean mass; adjusted R2u202f=u202f0.19, pu202f=u202f0.036 for leg lean mass). There was no difference in TBS when patients were grouped by fracture status, anticonvulsant use, gonadal status or use of PEG feeding. TBS was lower in non-ambulatory patients compared with ambulatory patients (1.28 vs 1.37, pu202f=u202f0.019).nnnCONCLUSIONSnAbnormal bone microarchitecture, as measured by TBS, was seen in >50% of young adults with CP. TBS correlated with both areal BMD and appendicular lean mass. Maintaining muscle function is likely to be important for bone health in young adults with CP and needs to be confirmed in further studies.