Papers by Keyword: Bisphosphonates

Abstract: Bisphosphonates currently represent the main therapy in the fight against osteoporosis. This is a serious condition, with an increasing incidence, presently affecting about 12 million people in the U.S. mostly women aged over 50 years. Thus, approximately 40% -50% of them suffer an osteoporotic fracture. Bisphosphonates mechanism of action consists in reducing osteoclast-mediated bone resorption, modifying bone turn over, leading to an increase in bone density. This dramatically reduces the risk of fracture. Although bisphosphonates shows a good safety profile, lately emerged some alarm signals that link their long management to some unusual side effects. Bisphosphonates is an effective therapy to combat osteoporosis, their causal relationship with FAF production not being shown. In the absence of other evidence, it is unclear whether BF therapy is directly involved in producing FAF or only a component of a combination of factors, in reality being just an indicator of a severe degree of osteoporosis. In the same time, we must not forget that the FAF are very rare compared to the number of patients in therapy with BF and the number of typical femur fractures, and the risk / benefit ratio it is definitely in favor of the benefit.

Abstract: The integration of drugs and devices is a growing force in the medical industry. The incorporation of pharmaceutical products not only promises to expand the therapeutic scope of device technology but to access combination products whose therapeutic value stem equally from both the structural attributes of the device and the intrinsic therapy of the drug. For example, the orthopedic industry is exploring drug-coated hip, knee and bone reconstruction implants capable of promoting healing as an added therapeutic benefit for device recipients. In this context, the drug is eluted locally, being targeted in a specific site of interest, thus offering a convenient strategy to avoid adverse effects commonly observed for systemic treatments of some diseases, as an additional benefit. In addition, these new technologies are generally well adapted to the development of minimally invasive surgery for their implantation. In this context, given the wide use of calcium phosphates (CaPs) and bisphosphonates (BPs) for the therapy of bone-related affections, there was great interest to investigate the chemistry taking place when combining the two systems since: (i) it could provide better insight in the mechanism of BP fixation on bones (ii) such combination could act as efficient BP delivery systems when implanted in bone defects.

Abstract: Bisphosphonates (BPs) may play an important role in minimizing osteolysis. In this work two new bisphosphonates pertaining to second and third generations respectively, have been synthesized and incorporated onto a chemically enriched hydroxyapatite. BP synthesis has been performed by adding H3PO3, PCl3 and methanesulfonic acid over 4-aminophenyl acetic acid (APBP) and 1-H-indole-3-acetic acid (IBP) respectively at 65°C in a N2 atmosphere. These compounds bear a primary amine group bonded to an aromatic ring, and a secondary amine group within a heterocyclic ring respectively. A chemically enriched hydroxyapatite with a chemical content corresponding to a 50% fluorided hydroxyapatite has been synthesized. Ceramic bodies manufactured by uniaxial pressure followed by cold isostatic press have a 97% density and submicron grain size. The BP was adsorbed onto the surface by immersion in a stirred solution at 37°C for 48 hours. A 10-fold decrease of the surface energy was observed for bodies modified with the APBP whereas only a 25 % decrease is obtained for bodies loaded with the bisphosphonate loaded with the IBP.

Abstract: Hydroxyapatite has been frequently described as an osteoconductive but not osteoinductive material based on failure to observe bone formation in nonbony sites. Bisphosphonates (BPs) are stable pyrophosphate analogs, that enhance the proliferation, differentiation and bone forming activity of osteoblasts and are potent inhibitors of bone resorption. In this paper, the modification of a calcium hydroxyfluor carbonate apatite with sodium alendronate and (4-(aminomethyl)benzene)bisphosphonic acid is described. The surface modification is carried out by refluxing the apatite in a bisphosphonate acetone solution. Modified particles are characterized by thermal analysis, ATR-IR spectroscopy and contact angle between other techniques. A weight loss between 150 and 500°C can be observed for the modified apatites. IR spectra show the appearance of bisphosphonate bands on modified powders. The surface energy of the modified apatite is reduced up to a 74% from the total apatite value after the alendronate surface modification with a decrease of 58% of the polar component main responsible of the cellular interaction of biomaterials.