Background: Rett Syndrome (RS) is a disabling condition due to mutations in MECP2. Girls affected with RS are at risk of developing osteoporosis and fractures at a young age because of their lack of mobility and through a direct effect of MECP2 on bone mineralization. In these girls, bone fragility inflicts pain and may seriously impair the quality of life.
Objective: To retrospectively assess the effect of IV bisphosphonates on fracture, bone mineral density (BMD) and bone markers in RS girls with bone fragility.
Methods: Once diagnosed with bone fragility and fracture and/or bone pain, RS girls received either 1.5 mg/kg of pamidronate IV every 3 months (n=16) or 0.04 mg/kg of zoledronate IV every 6 months (n=1) for 2 years. Results are shown as median [min; max].
Results: 20 patients were studied (age: 12.5 years [6; 39]). 14/20 patients were non ambulatory. The incidence of fracture decreased from 37 fractures in 20 patients (6 months interval preceding the start of therapy), to 0 fracture in 20 patients during or after IV bisphosphonates (follow-up: 3.1 years [2; 4.2]). The spine BMD Z-score improved from −3.2 [−5.6; −0.1] to −2.05 [−3.8; 0.0], P=0.0011. Most parents reported a decrease in chronic pain; 2 patients started to walk around the end of the 2-years therapy. The urinary calcium excretion, decreased significantly from 0.68 [0.18; 1.5] to 0.2 [0.03; 0.67] mM/mM of creatinine (P=0.0001). Except for moderate hypocalcemia and fever, pamidronate was well tolerated in all girls.
Conclusion: Our results are in accordance with the beneficial effect of bisphosphonates in children with cerebral palsy. Impaired bone mineralization in RS girls should be screened and prevented through measures including vitamin D supplements, nutritional support and careful mechanical loading. In girls experiencing fractures, IV bisphosphonates appear to be a beneficial adjuvant treatment to diminish the risk of fracture and restore the bone density.
Disclosure: The authors declared no competing interests.