196. Bone Marker Response in Chronic Diffuse Sclerosing Osteomyelitis Treated with Ibandronate

Background: CDSO is a condition affecting predominantly the mandible and long bones of young females, characterised by episodes of intractable pain on a background of chronic discomfort. The aetiology is unknown, but the bone sclerosis is associated with abnormal osteoblast and osteoclast function. Methods: We report 3 cases in which symptoms and biochemical markers responded to treatment with intravenous ibandronate. Results: Case one is a 27 yrs lady who had suffered episodes of pain in the left hip and thigh for 21 yrs, with cortical thickening of the femur on X-Ray and MRI, diagnosed with CDSO on bone biopsy. Treatment with oral bisphosphonates provided symptomatic relief for some years, but recently episodes of pain had increased in frequency and severity. She received 3 infusions of 2 mg ibandronate over 3 months, with good symptomatic relief. Case 2 is a 38 yrs old female with a 10 yrs history of pain in the left tibia, diagnosed with CDSO after X-ray, isotope bone scan and bone biopsy. Intrameduallary nailing and oral bisphosphonates provided temporary relief. She received 3 infusions of ibandronate 1 month apart, at a dose of 2 mg, 3 mg and 3 mg, with rapid and prolonged improvement in symptoms. Case 3 is 21 yrs old lady with a 5 yrs history of pain in the left femur and tibia. CDSO was confirmed by isotope bone scan and biopsy, and an intramedullary nail inserted in the femur, with little symptomatic benefit. She had little response to oral bisphosphonates or a course of intravenous pamidronate, but made a gradual and sustained response to 4 infusions of 2 mg ibandronate over 4 months. Conclusions: Although CDSO is thought to be predominantly a disease of bone deposition and osteoblast activity, bisphosphonates act primarily by inducing osteoclast apoptosis, although they may also have effects on osteoblasts. We have described a general fall in both osteoblast activity (ostase and osteocalcin) and osteoclast activity (serum crosslaps) in all three patients, with much higher initial osteoblast and osteoclast activity in patient three, who had the least impressive clincial response. Although only three patients are described, these findings suggest that the levels of bone markers vary significantly between patients, perhaps depending on previous therapy or extent of involvement, but that both osteoblast and osteoclast activity tend to fall after ibandronate therapy. A larger study is required to investigate the link between bone enzymes, disease activity and response to therapy, but we believe that intravenous ibandronate represents a novel treatment option in resistant cases of CDSO.