Long-term effects of bisphosphonate therapy in children with osteogenesis imperfecta

Andrew Biggin; Linda Zheng; Julie Briody; Mary McQuade; Craig Munns

doi:10.1530/boneabs.2.OP13

Objectives: To evaluate the clinical outcomes of intravenous bisphosphonate treatment in children with mild-moderate osteogenesis imperfecta (OI) who had progressed from active bisphosphonate treatment to maintenance therapy for >2 years.

Methods: A retrospective review was conducted on 17 patients with mild-moderate OI. Clinical data, fracture history, biochemistry, dual energy X-ray absorptiometry (DXA) parameters, vertebral measurements, bone age and metacarpal cortical thickness were collected at three time points: before treatment, following active treatment with high dose bisphosphonates and after establishment on a low dose maintenance treatment phase. Active treatment was defined as zoledronic acid 0.05 mg/kg 6-monthly or pamidronate 6–9 mg/kg per year. Maintenance treatment was defined as zoledronic acid 0.025 mg/kg 6-monthly or pamidronate <4 mg/kg per year.

Results: The mean age at commencement of active treatment was 4.8±2.6 years and progression to maintenance therapy was 10.0±2.6 years. Mean time on maintenance therapy was 4.1±1.4 years. Height Z-scores did not change significantly over time but weight Z-scores during active and maintenance treatment were higher than pre-treatment levels (see Table 1). There was a significant reduction in fracture rate when active treatment was commenced. This improvement was maintained during maintenance treatment. Biochemical analysis of bone homeostasis revealed a significant reduction in bone turnover markers between active and maintenance treatment.

DXA showed a significant improvement in bone mineral density (BMD), bone mineral content (BMC) and BMC for lean-tissue mass Z-scores. Vertebral height increased in both normal lumbar vertebrae (L1–L4) and fractured thoracic and lumbar vertebrae from pre-treatment to active therapy and was maintained during maintenance treatment. Assessment of hand X-rays showed that 2nd metacarpal cortical thickness and relative cortical area increased over the treatment periods.

Table 1 Mineral homeostasis, DXA data and bone morphometry
	Pre-treatment	Active	Maintenance
Height Z-score	−1.4±1.6	−1.3±1.7	−1.7±2.4
Weight Z-score	−1.2±1.6	0.1±1.5*	0.0±1.6*
Fracture rate (number/year)	1.5±1.1	0.7±0.7*	0.7±0.9*
Calcium (mmol/l)	2.43±0.10	2.35±0.07	2.30±0.07
Alkaline phosphatase (U/l)	277±63	210±46*	164±74*
Phosphorus (mmol/l)	1.61±0.17	1.50±0.13*	1.40±0.15*
Osteocalcin (nmol/l)	7.4±3.7	7.8±6.2	3.4±3.0*
25-OH-Vitamin D (nmol/l)	75±32	69±22	62±17
Urine Deoxypyridinoline:Cr ratio (nM/mM)	115±75	117±89	57±52
Total BMD Z-score	−0.9±1.2	−0.6±1.2*	−0.8±1.8
L1–L4 BMD Z-score	−2.5±1.2	−0.5±1.3*	−0.3±1.1*
Total BMC Z-score	−1.1±0.6	−0.7±1.5*	−0.9±1.9*
BMC for LTM Z-score	−1.4±1.1	0.2±1.7*	0.5±1.5*
Vertebral height (anterior:length ratio)	0.70±0.06	0.76±0.07*	0.76±0.09*
2nd Metacarpal relative cortical area	8.6±4.0	14.6±4.9*	21.8±6.5*
Values represent mean±S.D.,*Represents P<0.05 compared to pre-treatment values.

Conclusion: Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of a high dose active treatment regimen. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI.

Bone Abstracts

OP13