None listed
Conditions
Brief summary
Boys with Duchenne muscular dystrophy (DMD) have an increased risk of long bone and vertebral fracture due to reduced bone mass (osteopenia). In DMD, osteopenia is due to both reduced mobility and glucocorticoid use. There is no recognised treatment for osteopenia in DMD. Bisphosphonates are a class of drug which act primarily by decreasing the activity of the bone resorbing cells, the osteoclast. In children with osteogenesis imperfecta (brittle bone disease) bisphosphonates have been shown to improve bone strength and increase bone density (areal Bone Mineral Density (aBMD)) through a combination of increased cortical thickness and trabecular number. Bisphosphonates alter the course of corticosteroid induced bone loss and largely prevent this complication in the adult population. It is more difficult to provide such evidence in a paediatric population where linear growth and puberty both rapidly alter skeletal size and make interpretation of bone density more difficult. With techniques of volumetric bone density (BMAD) calculation available, more accurate data can now be observed. Study significance This study is powered to provide definitive data on the utility of 3-6 monthly intravenous zoledronic acid to improve bone density in boys with DMD. Results from this study will be used to develop a study to assess fracture reduction in this population. This in turn would have far reaching consequences in terms of potential reduction in morbidity, hospitalization and immobilization of affected boys.
Interventions
to assess whether zoledronic acid 0.025mg/kg/dose as an intravenous preparation infused over 30 minutes, at 0,3 months then 0.05mg/kg/dose at 6,12 and 18 months is superior to calcium as an oral tablet plus vitamin D as orally administered capsule, to improve bone density and reduce fracture risk in boys with Duchenne muscular dystrophy
Sponsors
Royal Children's Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
6 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
All boys between 6-16 years with confirmed Duchenne Muscular Dystrophy (DMD) and who are receiving glucocorticoid therapy (this is universally prednisolone)
Exclusion criteria
Genant Grade 3 or greater vertebral compression 1. Any prior use of osteoporosis or bone-modifying therapy, such as bisphosphonates, sodium fluoride, calcitonin, calcitriol, Gonadotrophin releasing hormone agonists or Growth Hormone (GH). 2. Patients who have received testosterone therapy may only be included in the trial if this therapy was given as part of physiological replacement in the setting of documented hormonal deficiencies 3. Any prior history of malignancy 4. Any medical condition that might interfere with the evaluation of LS BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable vertebrae by DEXA evaluation in the region of interest (ROI) L1-L4, as confirmed by the central imaging laboratory, will not be considered eligible for this study. 5. Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at screening 6. Vitamin D deficiency (serum 25-hydroxy vitamin D concentrations of < 50 nmol/L) at screening 7. Renal impairment: Glomerulr filtration rate (GFR) < 35 ml/min/1.73 m2 at screening based on the Schwartz formula. 8. A serum creatinine increase between Visit 1 and Visit 2 greater than 44.2 mmol/L 9. History of hyperparathyroidism, hypothyriodism or hyperthyroidism within 1 year of screening 10.History of sarcoidosis, primary bone disease (osteogenesis imperfecta, idiopathic juvenile osteoporosis, rickets/osteomalacia)., Kawasaki’s disease or Henoch-Schonlein Purpura. 11. Diagnosis of active uveitis (symptomatic or asymptomatic) at the time of enrollment of the study. 12. Any subject involved in another study, if an investigational agent is deemed by investigators to possible interfere with this study agent. ( for example use of a different bisphosphonate or a statin, a drug that utilizes the same biochemical pathways )
Outcome results
None listed