Is bisphosphonate-induced osteonecrosis of the jaw (BONJ) an ischemic manifestation of pseudo-osteopetrosis?: Biochemical, densitometric, and imaging evidence

Abstract

18621 Background: BONJ is an increasingly recognised but poorly understood complication of long-term B therapy. We hypothesise that the pathophysiology is ischaemic, and is due to an osteopetrosis (OP)-like lesion which causes progressive constriction of maxillo- mandibular perforating arterial foramina. Support for this comes from the observation that the osteoclast ruffled border is functionally impaired in osteopetrosis and structurally lost with B therapy. Cases of maxillomandibular osteomyelitis and avascular necrosis complicating OP exist. Additionally the blood supply of the jaw relies partly on small periosteal perforators. Methods: Bone mineral density (BMD) of 2 female patients (pt) with BONJ was investigated with dual energy x-ray absorbptiometry. Serum creatinine BB-isoenzyme (CK-BB) was determined. Serum acid phosphatase was assessed for patient 1. Bone biochemistry; (serum calcium, phosphate, parathyroid hormone, bone alkaline phosphatase, 25(OH) vitamin D, osteocalcin (intact), N. Ter.procoll1, CTX-1) was assessed. Multislice CT with orthoradial reconstruction was performed on pt 1. Results: CK-BB isoenzyme was increased at 21% and 20% in patients 1 and 2 (upper limit normal 2%). DEXA scan patient 1 results: BMD, lumbar spine; T score 4.9 (152%), Z score 5.4 (160%), femur; T score 2.2 (128%) Z score 2.5 (134%). DEXA scan patient 2 results: BMD lumbar spine; T score 0.2, Z score 1.2, femur; T score 1.2, Z score 1.8. Serum acid phosphatase in pt 1 was normal. Orthoradial reconstruction of the mandible in pt 1 showed absence of lateral lingual canals in affected hemi mandible.Mental foramen and inferior alveolar canal were not constricted. Conclusion: The increased BMD and CK BB isoenzyme seen in our pts are characteristic features of osteopetrosis. The normal acid phosphatase is explained by bisphosphonate-induced osteoclast apoptosis a phenomenon that does not occur in osteopetrosis. Orthoradial reconstruction of the mandible provided radiological correlation. The data was found to be consistent with the hypothesized disease process. No significant financial relationships to disclose.