Novel use of bisphosphonates to improve surgical outcomes in experimental bone tuberculosis

Tuberculous osteitis is a chronic, granulomatous bone infection that frequently results in impaired bone healing following surgery. Despite surgical intervention and prolonged anti-tuberculous therapy, complete bone regeneration often remains unachieved, contributing to subsequent orthopedic complications.

To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.

A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups: (1) Bisphosphonates alone; (2) Bisphosphonates combined with anti-tuberculous therapy; and (3) Anti-tuberculous therapy alone. The control group consisted of animals that received no surgical or medical treatment. Clinical evaluations, biochemical markers, micro-computed tomography imaging, and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.

Pamidronate treatment significantly reduced early implant resorption, increased osteoblastic activity, improved trabecular bone regeneration, and maintained graft integrity compared to the anti-tuberculous therapy-only group. Histologically, pamidronate led to enhanced vascular remodeling and increased bone matrix formation. Crucially, bisphosphonate therapy demonstrated safety, compatibility with anti-tuberculous medications, and did not exacerbate tuberculous inflammation. Furthermore, micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups, underscoring the anabolic effects of bisphosphonates. Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces. These combined radiological, histological, and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.

A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis. The following prospective studies are needed.