Bone Healing in Children With Osteogenesis Imperfecta Treated With Bisphosphonates

Abstract

The long-term effects of bisphosphonate treatment in children with osteogenesis imperfecta (OI) are unknown. The aim of this study was to evaluate whether treatment with bisphosphonates interferes with the healing of fractures in a group of children with OI. Seven subjects (6 boys), aged 11.4 +/- 5.95 years, were followed for 2.5 +/- 0.84 years after the start of treatment with intravenous pamidronate (9 mg/kg/y) and/or oral alendronate (5 or 10 mg/d). Orthopaedic surgery of 24 bones was performed after 2.33 +/- 4.14 months of treatment, with 1.6 +/- 0.84 osteotomies per bone. Ambulation was started after 26.1 +/- 32.28 days. Reoperation was required in 8% of the bones due to fracture below primary fixation. Pseudoarthrosis was seen in one fracture, an osteotomy of the proximal femur (14% of the patients, as expected in an OI population). These results suggest that treatment with bisphosphonates at the administered doses does not interfere with fracture healing. Larger and longer studies are warranted.

Pamidronate Treatment of Children with Moderate-to-Severe Osteogenesis Imperfecta: A Note of Caution

“…However, nonunion of spontaneous fractures occurred in as many as 8 (29.6%) of our patients. The definition of delayed fracture healing or nonunion is not agreed on [20]. We defined nonunion as absence of fracture healing after 6 months, in accordance with previous data [20].…”

“…Radiographs were taken to evaluate fracture healing. Delayed healing was defined as unhealed fracture after 6 months [20]. …”

“…Little is known about long-term safety, which is a matter of concern since bisphosphonates accumulate in bone, where they remain for many years. Experimental studies seem to support theoretical concerns that bisphosphonates may delay fracture repair by suppressing bone turnover [19], although several clinical studies found no increase in time to fracture healing [20, 21]. Pamidronate may increase cartilage calcification by suppressing resorption, and linear areas of increased bone density may develop [5], although the clinical significance of these changes is unclear.…”

Osteogenesis Imperfecta

“…Non-unions have been noted in 15% of children with osteogenesis imperfecta even prior to treatment with bisphosphonates (Agarwal and Joseph, 2005). There is one report of delay in healing following osteotomies but not fractures (Pizones et al, 2005). Non-unions have been reported post surgically (Cho et al, 2011).…”

Pathological mandibular fracture after simple molar extraction in a patient with osteogenesis imperfecta treated with alendronate

“…In comparison with healthy patients, fractures heal more rapidly but the newly formed bone is of the same inferior quality as the original one. Moreover, some reports suggest that there is no influence of bisphosphonate treatment on fracture healing, whereas others show a delay of fracture healing in animal models (16). In conclusion, particular care is necessary is these patients during oral surgery, even when they have been treated and controlled.…”