Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2–Dependent Rat Posterolateral Arthrodesis Model

Abstract

Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 μg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro–computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.

Engineered collagen-binding bone morphogenetic protein-2 incorporated with platelet-rich plasma accelerates lumbar fusion in aged rats with osteopenia

“…However, most authors performed their studies in young models whose osteopenia was induced by physical or chemical methods. 35,36 It is not reasonable to perform a study concerning an age-related disease in young body, whose physiological function, metabolic rate, and bone microenvironment are quite different from the aging body.…”

“Osteo-protective effect of Curcumin; Fenugreek and their combination on ovariectomized female rats”.

“…On the other hand, estrogen deficiency results in increased production of IL-7, leading to T cell activation. This is accompanied by an increased production of IFN-γ and TNF-α by T cells [15][16][17]. One major action of IFN-γ is the up-regulation of major histocompatibility complex (MHC) class II molecules on antigen presenting cells, such as Egypt.…”

Optimization of the Time Window of Interest in Ovariectomized Imprinting Control Region Mice for Antiosteoporosis Research

“…Deficiency of estrogen directly affects bone turnover by stimulating osteoclast activity and inhibiting osteoblast activity [ 8 , 9 ]. Female OVX rats, which mimic the postmenopausal hormonal changes that occur in humans [ 10 ], are currently the most widely used animal models to evaluate changes in the trabecular bone architecture, serum indices after ovariectomy, and treatment results of antiosteoporotic drugs [ 11 , 12 ]. However, although mouse models require less money and medical resources, especially drugs that are difficult to purify and synthesize, few systematic studies have been performed on mouse models of osteoporosis.…”