Hypermobile Ehlers-Danlos syndrome (EDS) is a heterogenous genetic disorder that affects collagen synthesis and is associated with increased bone fragility and low bone mass due to abnormal bone microarchitecture. Currently, no therapeutic guidelines exist with regards to screening and managing skeletal fragility in patients with EDS. The efficacy of sclerostin inhibitors such as romosozumab has not been determined. Here we present a rare case of a 23-year-old male with congenital hypermobile EDS and a 10-year history of reasonably controlled type 1 diabetes with no established complications presenting with severe osteoporosis managed with romosozumab.
The patient initially presented with acute back pain following a hypoglycaemic seizure, prompting further investigation to reveal an osteofragility fracture of his thoracic vertebrae. Physical examination revealed marked joint hypermobility, hyperelastic skin, and reduced muscle strength. Bone densitometry confirmed osteoporosis with a significantly reduced bone mineral density at the lumbar spine of 0.748g/cm² (Z-score -4.1) and total hip 0.702g/cm² (Z-score -2.9). Laboratory analysis revealed 25-OH vitamin D deficiency (32nmol/L), elevated bone turnover (CTx 940ng/L, RR:400-900ng/L) and reasonable diabetic control (Hba1c 7.4%). Coeliac and myeloma screening were negative.
Osteoporosis therapy was initiated with oral colecalciferol 5000IU daily and privately-funded romosozumab 210mg monthly subcutaneous injections. Follow-up at six months showed a significant 12.6% increase in his lumbar spine bone mineral density to 0.842g/cm² (Z-score -3.0) and a 13.1% increase in bone density of his total hip 0.785/cm² (Z-score -2.3). CTx bone turnover marker also improved (490ng/L). Diabetic management was achieved using a Tandem t:slim insulin pump with Dexcom G6 continuous glucose monitoring as well as dietary adjustments to avoid hypoglycaemia.
This case highlights the complex nature of osteofragility fractures in young adults with EDS as well as our patient’s marked response to romosozumab. It warrants further investigation as a potential treatment option for patients with EDS and osteoporosis.