Abstract
BackgroundPatients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature. Dual-energy X-ray absorptiometry (DXA) is the current gold standard for clinical assessment of bone in the general population and has been adopted for monitoring bone density in IBEM patients. However, IBEM patients are at greater risk for scoliosis, short stature and often have orthopedic hardware at standard DXA scan sites, limiting its use in these patients. Furthermore, DXA is limited to measuring areal bone mineral density (BMD), and does not provide information on microarchitecture.MethodsIn this study, microarchitecture was investigated in IBEM patients (n = 101) using a new three-dimensional imaging technology high-resolution peripheral quantitative computed tomography (HR-pQCT) which scans at the distal radius and distal tibia. Volumetric BMD and bone microarchitecture were computed and compared amongst the different IBEMs. For IBEM patients over 16 years-old (n = 67), HR-pQCT reference data was available and Z-scores were calculated.ResultsCortical bone density was significantly lower in IBEMs associated with decreased bone mass when compared to lysosomal storage disorders (LSD) with no primary skeletal pathology at both the radius and tibia. Cortical thickness was also significantly lower in these disorders when compared to LSD with no primary skeletal pathology at the radius. Cortical porosity was significantly greater in hypophosphatasia when compared to all other IBEM subtypes.ConclusionWe demonstrated compromised bone microarchitecture in IBEMs where there is primary involvement of the skeleton, as well as IBEMs where skeletal complications are a secondary outcome. In conclusion, our findings suggest HR-pQCT may serve as a valuable tool to monitor skeletal disease in the IBEM population, and provides insight to the greatly varying bone phenotype for this cohort that can be used for clinical monitoring and the assessment of response to therapeutic interventions.
Highlights
Patients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature
A high risk of fractures has been reported in IBEMs where there is primary involvement of the skeleton, such as HPP and osteogenesis imperfecta
There are important limitations of using Dual-energy X-ray absorptiometry (DXA) as a basis for measuring bone density, and high-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging alternate technology that provides three-dimensional assessment of bone microarchitecture and associated bone strength that is useful in these complex bone phenotypes
Summary
Patients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature. Dual-energy X-ray absorptiometry (DXA) is the current gold standard for clinical assessment of bone in the general population and has been adopted for monitoring bone density in IBEM patients. IBEM patients are at greater risk for scoliosis, short stature and often have orthopedic hardware at standard DXA scan sites, limiting its use in these patients. Common symptoms include growth disturbances, endocrine dysfunction, neurological abnormalities, and musculoskeletal complications. Musculoskeletal complications inhibiting physical functioning have been mentioned to be the one of the most debilitating aspects of the disorder by parents of diagnosed children [4]. Imaging plays an important clinical role in diagnosis and evaluation of severity and activity of skeletal disease, as well as monitoring treatment effect [5]
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