Tohoku J. Exp. Med., 2021 April, 253(4)

Morphological and Morphometrical Analyses of Fracture-Healing Sites of an Atypical Femoral Fracture in Patients with and without Long-Term Bisphosphonate Treatment for Osteoporosis: A Report of Two Cases

Takashi Aki,1 Ko Hashimoto,1 Hiroaki Uozumi,2 Masahiro Saito,3 Ko Sugawara,4 Manabu Suzuki,1 Soshi Hamada,1 Akemi Ito5 and Eiji Itoi1

1Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
2Omagari Orthopaedic Clinic, Omagari, Akita, Japan
3Department of Pathology, Hiraka General Hospital, Yokote, Akita, Japan
4Sugawara Orthopaedic Clinic, Ichinoseki, Iwate, Japan
5Ito Bone Histomorphometry Institute, Niigata, Niigata, Japan

Bisphosphonates have been the first drug of choice for osteoporosis in the recent years because of their known ability to suppress osteoclast activity. The adverse effect of long-term bisphosphonate administration in the fracture-healing process is controversial. The aim of our study was to observe not only morphology but also morphometry of the fracture site of atypical femoral fracture with and without long-term bisphosphonate administration, in a case study of two difficult-to-obtain human samples. The patients with insufficient healing of atypical femoral fracture were treated with valgus wedge osteotomy. Histomorphometrical analysis was performed in bone samples of fracture sites harvested during osteotomy. The thickness of the femoral cortex was measured in the fracture site and the adjacent, non-fracture site. A comparative analysis of the content of hypertrophic osteoclasts in fracture sites, shape and size of osteons, mass, and ratio of the woven bone to the total bone mass was performed, comparing bisphosphonate-treated and untreated samples. In bisphosphonate-treated samples, we observed femoral cortex thickening at the fracture site; the appearance of hypertrophic osteoclasts; decreased bone resorption surface, decreased osteoclast numbers on the bone resorption surface, and increased ratio of multinuclear osteoclasts; osteons were misshapen and thin; and the mass and ratio of the woven bone to the total bone mass were higher. This study demonstrated that long-term bisphosphonate administration can alter the morphological features of the fracture site compared to its physiological state.

Key words —— atypical femoral fracture; bisphosphonates; bone morphology; fracture healing; long-term therapy


Tohoku J. Exp. Med 2021, 253, 261-267.

Correspondence: Ko Hashimoto M.D., Ph.D., Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.


*These two authors contributed equally to this work.