Risk factors for poor bone health in primary mitochondrial disease

Abstract

Introduction Primary mitochondrial disease is caused by either mitochondrial or nuclear DNA mutations that impact the function of the mitochondrial respiratory chain. Individuals with mitochondrial disorders have comorbid conditions that may increase their risk for poor bone health. The objective of this retrospective electronic medical record (EMR) review was to examine risk factors for poor bone health in children and adults with primary mitochondrial disease. Methods 80 individuals with confirmed clinical and genetic diagnoses of primary mitochondrial disease at the Children’s Hospital of Philadelphia (CHOP) were included in this study. Risk factors and bone health outcomes were collected systematically, including: anthropometrics (low BMI), risk-conferring co-morbidities and medications, vitamin D status, nutrition, immobility, fracture history, and, where available, dual energy x-ray absorptiometry (DXA) bone mineral density (BMD) results. Results 73% (n=58) had at least one risk factor and 30% (n=24) had four or more risk factors for poor bone health. The median number of risk factors per participant was 2, with an interquartile interval (IQI 0–4). In the subset of the cohort who were known to have sustained any lifetime fracture (n=11), a total of 16 fractures were reported, 6 of which were fragility fractures, indicative of a clinically significant decrease in bone strength. Conclusions The prevalence of risk factors for poor bone health in primary mitochondrial disease is high. As part of supportive care, practitioners should address modifiable risk factors to optimize bone health, and have a low threshold to evaluate clinical symptoms that could suggest occult fragility fracture.

Height as a Clinical Biomarker of Disease Burden in Adult Mitochondrial Disease

“…As well as gastrointestinal symptoms, patients with mitochondrial disease may have other comorbidities that could theoretically affect growth and bone health (9, 32, 33). These include endocrinopathies such as hypoparathyroidism, hypothyroidism, and diabetes.…”

“…Patients with severe mitochondrial disease are more likely to be receiving multiple medications, which may also affect growth; however, because the majority of our patients attained final height before overt disease onset, this potential mechanism is unlikely. The prevalence of one risk factor affecting bone health in mitochondrial disease was estimated at 73% in one cohort, with 30% having four risk factors (33). Patients with mitochondrial disease are at elevated risk of osteoporosis, with more than half of the adult population known to have at least one risk factor (31).…”

Comparative proteomics analysis reveals the difference during antler regeneration stage between red deer and sika deer

“…The three key subunits of COX are synthesized in mitochondrial to form the functional core of the enzyme, which is surrounded by 11 small nuclear-coded subunits (Balsa et al, 2012). The activity of cytochrome c oxidase, complex IV of the mitochondrial respiratory chain, has been shown to regulate the activity of osteoclasts necessary for adaptive bone remodeling (Gandhi et al, 2017; Miyazaki et al, 2003). The disruption of osteoclast COX activity could lead to the loss of bone-resorbing activity.…”

Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

“…We established SHEDs derived from a 6-year-old boy diagnosed with LS (LS-SHEDs) caused by a G13513A mutation in the mtDNA encoding the ND5 subunit of respiratory chain complex I [ 116 ]. Patients with LS are predominantly characterized by neuropathology, but other organs, including bone, are also severely affected [ 117 , 118 ]. However, the direct effects and molecular mechanisms of mitochondrial dysfunction on bone health have not been extensively elucidated.…”