The effect of ultraviolet photofunctionalization of titanium instrumentation in lumbar fusion: a non-randomized controlled trial.

BACKGROUND: Titanium instrumentations are widely used in orthopedics; the metal bonds with bone in a process called osseointegration. Over time, hydrocarbons adhere to the instrumentation, which weakens the bone-binding ability. Ultraviolet photofunctionalization enhances the bone-binding ability of instrumentation by reducing hydrocarbons. The process has been proven effective in dentistry, but its effects in orthopedics are unverified. We aimed to determine the effect of ultraviolet photofunctionalization of titanium instrumentation used in lumbar fusion. METHODS: This was a non-randomized controlled trial. We prospectively enrolled 13 patients who underwent lumbar fusion surgery. We inserted two pure titanium cages into each intervertebral space; one cage had undergone ultraviolet photofunctionalization, while the other was untreated. The degree of osteosclerosis around both cages was then compared by measuring the densities around the cages on imaging at 2, 3, 6, and 12 months postoperatively compared with 1 month postoperatively. The carbon attachment of the titanium cages was measured using X-ray photoelectron spectroscopy. RESULTS: There was no significant difference between the degree of osteosclerosis (as assessed by the density) around the treated versus untreated cages at any timepoint. The ratio of carbon attachment of the titanium cages was only 20%, which was markedly less than the ratio of carbon attachment to titanium instrumentation previously reported in the dentistry field. CONCLUSIONS: The effect of ultraviolet photofunctionalization of titanium instrumentation in spine surgery is questionable at present. The biological aging of the titanium may be affected by differences in the manufacturing process of orthopedics instrumentation versus dentistry instrumentation. TRIAL REGISTRATION: UMIN Clinical Trials Registry (Identifier: UMIN000014103 ; retrospectively registered on June 1, 2014).

Bone metastasis: histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review.

The development of a bone metastasis involves interactions between the tumor cells, the bone marrow microenvironment and the bone cells themselves. A better understanding of the pathophysiological changes occurring in bone metastasis can be obtained from histopathological examination of invaded specimens. This review focuses on the main molecular mechanisms implied in the localization and growth of malignant cells in the bone marrow. The corresponding histologic developmental stages are illustrated both in osteolytic (or mixed metastasis) or in the osteosclerotic forms by histological analysis, immunohistochemistry and microcomputed tomographic analysis of bone samples. In both cases, the malignant cells find a "fertile soil" in the bone marrow microenvironment. They use the growth factors released by bone cells for the coupling between osteoclasts/osteoblasts to promote their own development. In turn, they elaborate a variety of cytokines that can promote osteoclastogenesis (PTHrP, IL-1, IL-6…) or on the contrary, other growth factors that can boost the osteoblastic activity (ET1, IGFs). A "vicious circle" occurs between the malignant cells and the bone cells leading to the radiological expression of the metastasis.

Inhibition of necrotic actions of nitrogen-containing bisphosphonates (NBPs) and their elimination from bone by etidronate (a non-NBP): a proposal for possible utilization of etidronate as a substitution drug for NBPs.

PURPOSE: Nitrogen-containing bisphosphonates (NBPs) have powerful anti-bone-resorptive effects (ABREs). However, recent clinical applications have disclosed an unexpected side effect, osteonecrosis of the jaw. We previously found in mice that etidronate (a non-NBP), when coadministered with alendronate (an NBP), inhibited the latter's inflammatory effects. However, etidronate also reduced the ABRE of alendronate. The present study examined in mice the modulating effects of etidronate on the inflammatory and necrotic actions of zoledronate (the NBP with the strongest anti-bone-resorptive activity and the highest incidence of osteonecrosis of the jaw) and on ABREs of various NBPs including zoledronate. MATERIALS AND METHODS: NBPs were subcutaneously injected into ear pinnas of mice and ensuing inflammation and necrosis at the site of the injection were evaluated. ABREs of NBPs were evaluated by analyzing sclerotic bands induced in mouse tibias. RESULTS: Coinjection of etidronate reduced inflammatory and necrotic reactions induced by zoledronate, and also reduced the amount of zoledronate retained within the ear tissue. When both agents were intraperitoneally injected, etidronate reduced the ABRE of zoledronate and those of other NBPs. Notably, etidronate reduced the ABRE of zoledronate even when this non-NBP was injected 16 hours after the injection of zoledronate. Bone scintigram indicated that etidronate reduced the amount of zoledronate that had already bound to bone. CONCLUSIONS: These results suggest that etidronate may 1) inhibit the entry of NBPs into cells related to inflammation and/or necrosis, 2) inhibit the binding of NBPs to bone hydroxyapatite, 3) at least partly eliminate (or substitute for) NBPs that have already accumulated within bones, and thus 4) if used as a substitution drug for NBPs, be effective at treating or preventing NBP-associated osteonecrosis of the jaw.

[Pathophysiology of bone metastases]. / Pathophysiologie des métastases osseuses.

The aim of this review is to detail the pathophysiologic mechanisms occurring during bone metastases. osteolytic and osteosclerotic metastases are observed after migration of malignant cells coming from a primitive tumour which can localize and grow inside the hematopoietic bone marrow. Bone lesions observed during hematologic malignancies (lymphomas and myeloma) are not detailed here. The various cytokine networks that are occurring in bone metastases are detailed: in both cases there is a "vicious circle" between the the tumoral cells and bone cells responsible for the physiological remodeling of bone. The knowledge of these interferences permits to understand the use of anti-osteoclastic treatments (bisphosphonates) in osteolytic as well as osteosclerotic metastases.

Regulating DeltaFosB expression in adult Tet-Off-DeltaFosB transgenic mice alters bone formation and bone mass.

The DeltaFosB isoforms are naturally occurring AP-1 family members that increase bone volume via a cell-autonomous effect on osteoblastic bone formation. Mice overexpressing DeltaFosB demonstrate a very high level of bone formation, resulting in a progressive osteosclerosis. Despite the linkage of bone formation and resorption in physiological systems, no alteration in bone resorption was detected in mice overexpressing DeltaFosB. To determine whether altering DeltaFosB expression can regulate bone formation independently of bone resorption in adult mice, we used the Tet-Off-inducible transgene system to induce or block transgenic DeltaFosB overexpression and thereby regulate bone formation in vivo. Overexpression of DeltaFosB after skeletal maturity increased trabecular bone volume by increasing bone formation, again without altering bone resorption, indicating that developmental DeltaFosB overexpression is not required for the osteosclerotic phenotype. Similarly, switching off DeltaFosB overexpression after osteosclerosis had developed led to a marked decrease in bone formation and loss of bone mass such that trabecular bone volume approached normal levels. Despite this dramatic reduction, no alteration in bone resorption was detected. These results clearly demonstrate that DeltaFosB regulates bone formation and bone mass in adult mice with no effect on bone resorption.

Decrease of osteosclerosis in subchondral bone of medial compartmental osteoarthritic knee seven to nineteen years after high tibial valgus osteotomy.

Osteosclerosis of the subchondral bone was measured by densitometer on plain radiographs in 55 medial compartmental osteoarthritic knees of 40 patients who were treated with high tibial valgus osteotomy for correction of varus deformity. The ratio of the osteosclerosis value of the medial side of the knee to that of the lateral side (Medial/Lateral ratio) was calculated and used as a parameter. The Medial/Lateral ratio of osteosclerosis decreased rapidly within three years after osteotomy at the reference points of the femur and the tibia. Even 7 to 19 years after osteotomy, a decrease of the ratio was noted in 16 knees with a standing femorotibial angle (FTA) less than 168 degrees (12 degrees of anatomical valgus angulation). This was interpreted to mean that osteosclerosis of the medial condyle decreased compared with that of the lateral condyle after overcorrection of varus deformity. In the cases of more than 7 years after high tibial osteotomy, a positive straight regression line was drawn by calculation between Medial/Lateral ratio and postoperative limb alignment expressed by standing femorotibial angle, with coefficient of correlation (gamma) of 0.295 (p < 0.01).

Use of bisphosphonates for the treatment of bone metastasis in experimental animal models.

Therapeutic effectiveness of bisphosphonates (BP) on bone metastases in patients with cancers including those of the breast and prostate has been well documented. However, there are still many important questions that remain unsolved or controversial. To obtain answers for these questions that are not readily addressed in a well-controlled manner in clinical studies, we have developed two animal models of bone metastasis (orthotopic and experimental). Using these models, we studied the effects of BP alone or in combination with anti-cancer agents on the metastasis of breast cancer to bone and visceral organs. In addition, we also determined the effects of BP on osteosclerotic metastases. We found that BP impaired the progression of bone metastases primarily through enhancing apoptosis in osteoclasts and breast cancer cells colonized in bone. In some situations, however, BP alone increased metastases in visceral organs including liver and adrenal glands. However, combination of BP with anti-cancer agents enhanced the suppression of tumour in both bone and visceral organs, leading to prolonged survival of tumour-bearing animals. Of potential importance, preventative administration of BP inhibited the development of eventual osteosclerotic bone metastases. These results suggest that BP exhibits diverse beneficial effects on osteolytic and osteoblastic bone metastasis and non-bone organ metastasis in breast cancer when administered appropriately. They also suggest that the animal models of bone metastasis described here allow us to produce clinically- relevant information that is useful for the design of optimal regimens of BP for the treatment of breast cancer patients with bone and visceral metastases.