Bone Turnover in Patients with Lysosomal Storage Disorders

Background and aim: Lysosomal storage disorders (LSD) are inherited metabolic disorders which have skeletal involvement causing significant morbidity. Bone involvement is characterised by typical deformities, osteopenia/osteoporosis, pathological fractures, and bone marrow infiltration (avascular osteonecrosis, infarction). Estimation of skeletal disease includes bone quality that contributes substantially to bone strength. Bone mineral density (BMD) is a good indicator of bone status, but bone turnover markers (BTM) are valuable indicators of dynamic bone remodelling. The by-products of bone turnover may provide insight into acute bone metabolism including resorption by osteoclasts and formation by osteoblasts. Gold-standard markers are C-terminal telopeptide of type 1 collagen (CTx) for resorption and procollagen type-1 amino-terminal propeptide (P1NP) for formation. We aimed to analyze BTM and BMD in lysosomal storage disorders and predict bone status.

Method: A total of 24 children and adults aged 3 to 52 years with LSD who have been followed up for more than 1 year were included. BMD and selected BTM parameters including one formation marker P1NP and one resorption marker CTx were evaluated. Serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and 25-OH vitamin D levels were also measured.

Results: In total, 24 patients with LSD were included, of which, 5 (20.8%) were Gaucher patients and 19 (79.2%) were MPS patients. The mean patient age was 14.14 ±12.67 years, with 18 patients under the age of 18. The mean serum 25-OH vitamin D level was 25.12±16.33 µg/mL, the serum calcium level was 9.64±0.44 mg/dL, the serum phosphorus level was 4.60±0.66 mg/dL, and the ALP level was 168.95±96,37 mg/dL; all within normal limits. The mean Z score of the patients under the age of 18 was (-2.49)±(-2.05). T scores of adult patients were low. CTx levels of two adult patients were higher than average for their age (33%). CTx levels of four patients under the age of 18 were higher than the average for their age (22%).

Conclusion: This is the first study to analyse bone turnover markers of LSD. It was not possible to evaluate the bone density due to the bone involvement of the LSD. BMD measurement had low reliability and it may be difficult to distinguish between age-related osteoporosis and disease involvement in adults. BTM may predict bone status with CTx and P1NP indicating bone resorption/formation and may exclude bone involvement in the disease.