Our experience in the treatment of osteogenesis imperfecta with bisphophates

Introduction: Severe Osteogenesis Imperfecta (OI) or brittle bones disease is a heterogenic, congenital disease of the tissue which present clinically by an increased fragility or progressive deformity of the bones. At present it is not possible to treat OI. Since severe osteopenia or secondary osteoporosis are important symptoms of OI, the anti-resorptive activity of amino-bisphosphates can improve the clinical outcome in sick children. Aim: to assess the clinical affect of the use of amino-bisphosphates in Croatian children with brittle bones disease. Method: We began treatment in 1998 at the request of and with the informed consent of the parents of sick children from the Croatian Osteogeneis Imperfecta Association (HUOI). We now report the results of the treatment with intravenous pamidronates (APD) for 1.9 to 3.5 years in six children (four girls) with severe forms of OI, from 3 months to 11 years in age at the beginning of the treatment. Pamidronates are applicable in cycles of one day infusions once a month in doses of 1 –1.5 mk/kg over 6 months after which there is a break of 3 months, or the same dosage is given for 3 days every 4 months, to make it more appropriate to each child and family. They all took 500 to 1000 mg. calcium or supplement and 1000 iu vitamin D daily. At each visit the metabolic parametres of calcium were determined and the safety of the drug. Changes in bone mineral density (BMD) of the lumbar vertebrae (L1- L4) were expressed as absolute values, “real density” in g/cm2 and relative values for the age and sex of the corrected Z score were measured by dual- X - ray absorbsiometry (DEXA) on the same machine (QDR- 4500 W, Hologic), before treatment and once a year during the treatment. The indicators of bone rotation were carried out at the beginning of treatment but later were monitored irregularly due to financial problems. Results: During treatment, DEXA measurements showed a gradual and significant growth in bone mass in all the patients. Biochemical indicators of bone alterations showed decreasing bone disintegration. The number of fractures confirmed by X ray was significantly lower in all patients. The reduction in pain and the overall improvement in bone health and strength were impressive in the two boys who had been bound to their wheel chairs and can now walk with the aid of crutches. Apart from the well known reaction of acute inflammations (a syndrome similar to mild flu) during the first infusion cycle and mild asymptomatic hypocalcemia in two children, we did not notice any other clinical or laboratory side effects. During treatment in three children an increase in appetite was noticed with an excessive growth in body weight to height. Conclusion: Although bisphosphates do not correct the fundamental disorder in OI, they significantly help to change the natural course of the disease and improve the quality of life for sick children. For now it appears that they are not only effective but also relatively safe and with no harmful effects on the growth of the bones and remodelling. There are still a great many unanswered questions linked to the long-term effects of bisphosphates on the growing skeleton, but sick children cannot wait for better evidence.