Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles

We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT), The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally, The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry, The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02), This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone. (C) 2001 by Elsevier Science Inc. All rights reserved.

Osteoporotic hip fractures: Bisphosphonates sales and observed turning point in trend. A population-based retrospective study

The aim is to examine the temporal trends of hip fracture incidence in Portugal by sex and age groups, and explore the relation with anti-osteoporotic medication. From the National Hospital Discharge Database, we selected from 1st January 2000 to 31st December 2008, 77,083 hospital admissions (77.4% women) caused by osteoporotic hip fractures (low energy, patients over 49 years-age), with diagnosis codes 820.x of ICD 9-CM. The 2001 Portuguese population was used as standard to calculate direct age-standardized incidence rates (ASIR) (100,000 inhabitants). Generalized additive and linear models were used to evaluate and quantify temporal trends of age specific rates (AR), by sex. We identified 2003 as a turning point in the trend of ASIR of hip fractures in women. After 2003, the ASIR in women decreased on average by 10.3 cases/100,000 inhabitants, 95% CI (− 15.7 to − 4.8), per 100,000 anti-osteoporotic medication packages sold. For women aged 65–69 and 75–79 we identified the same turning point. However, for women aged over 80, the year 2004 marked a change in the trend, from an increase to a decrease. Among the population aged 70–74 a linear decrease of incidence rate (95% CI) was observed in both sexes, higher for women: − 28.0% (− 36.2 to − 19.5) change vs − 18.8%, (− 32.6 to − 2.3). The abrupt turning point in the trend of ASIR of hip fractures in women is compatible with an intervention, such as a medication. The trends were different according to gender and age group, but compatible with the pattern of bisphosphonates sales.

What impact do systemically administrated bisphosphonates have on oral implant therapy? A systematic review.

OBJECTIVES: The aim of this systematic review is to evaluate, analysing the dental literature, whether: * Patients on intravenous (IV) or oral bisphosphonates (BPs) can receive oral implant therapy and what could be the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ)? * Osseointegrated implants could be affected by BP therapy. MATERIAL AND METHODS: A Medline search was conducted and all publications fulfilling the inclusion and exclusion criteria from 1966 until December 2008 were included in the review. Moreover, the Cochrane Data Base of Systematic Reviews, and the Cochrane Central Register of Controlled Trials and EMBASE (from 1980 to December 2008) were searched for English-language articles published between 1966 and 2008. Literature search was completed by a hand research accessing the references cited in all identified publications. RESULTS: The literature search rendered only one prospective and three retrospective studies. The prospective controlled non-randomized clinical study followed patients with and without BP medication up to 36 months after implant therapy. The patients in the experimental group had been on oral BPs before implant therapy for periods ranging between 1 and 4 years. None of the patients developed BRONJ and implant outcome was not affected by the BP medication. The three selected retrospective studies (two case-controls and one case series) yielded very similar results. All have followed patients on oral BPs after implant therapy, with follow-up ranging between 2 and 4 years. BRONJ was never reported and implant survival rates ranged between 95% and 100%. The literature search on BRONJ including guidelines and recommendations found 59 papers, from which six were retrieved. Among the guidelines, there is a consensus on contraindicating implants in cancer patients under IV-BPs and not contraindicating dental implants in patients under oral-BPs for osteoporosis. CONCLUSIONS: From the analysis of the one prospective and the three retrospective series (217 patients), the placement of an implant may be considered a safe procedure in patients taking oral BPs for <5 years with regard to the occurrence of BRONJ since in these studies no BRONJ has been reported. Moreover, the intake of oral-BPs did not influence short-term (1-4 years) implant survival rates.

Care Required When Using Bisphosphonates in Dental Surgical Practice

Bisphosphonates are pharmacologic compounds characterized by high tropism to bone tissue. They affect bone metabolism by inhibition of osteoclast recruitment, proliferation, differentiation, and function. Because they can reduce bone resorption, bisphosphonates are used mainly for the treatment of osteometabolic conditions. However, the use of bisphosphonates has been associated with the onset of osteonecrosis of the jaws and indication of dental implants. As a result of this, the aim of this study was to present the risks and the care that health professionals should take in cases of surgical procedures such as placement of dental implants in patients who make use of bisphosphonates.

Management of Osteonecrosis of the Jaws in Patients With History of Bisphosphonates Therapy

Bisphosphonates are compounds used in the treatment of various metabolic and malignant bone diseases. The relation between the use of bisphosphonates and ostenonecrosis of the jaws as an adverse effect of the drug has been intensely discussed during the last few years, and up to this moment, there is no consensus concerning an ideal treatment modality for this condition. Nevertheless, there is an agreement among researchers that the standard goal for controlling jaw osteonecrosis is to prevent it. Otherwise, the rationale for a randomized controlled trial is that current treatment has proven to be suboptimal, and no consensus has been reached yet on the best strategies to repair the exposed bone once bone necrosis is developed. This article is focused on reporting a case of moderate osteonecrosis of the upper jaw induced by bisphosphonates and discusses a possible role for surgical debridement associated to platelet-rich plasma, hyperbaric oxygen therapy, and the cessation of the bisphosphonate use in managing this type of lesion. Moreover, the dentist, the oral surgeon, and the oncologist need to work together to reach better outcomes.

Bisphosphonates adherence for treatment of osteoporosis

Background: Osteoporosis is a disease of bone metabolism in which bisphosphonates (BPS) are the most common medications used in its treatment, whose main objective is to reduce the risk of fractures. The aim of this study was to conduct a systematic review on BPs adherence for treatment of osteoporosis. Methods. Systematic review of articles on BPs adherence for treatment of osteoporosis, indexed on MEDLINE (via PubMed) databases, from inception of databases until January 2013. Search terms were Adherence, Medication (MeSH term), Bisphosphonates (MeSH term), and Osteoporosis (MeSH term). Results: Of the 78 identified studies, 27 met the eligibility criteria. Identified studies covered a wide range of aspects regarding adherence and associated factors, adherence and fracture, adherence and BPs dosage. The studies are mostly observational, conducted with women over 45 years old, showing low rates of adherence to treatment. Several factors may influence adherence: socio-economic and cultural, participation of physicians when guidance is given to the patient, the use of bone turnover markers, and use of generic drugs. The monthly dosage is associated with greater adherence compared to weekly dosage. Conclusions: Considering the methodological differences between the studies, the results converge to show that adherence to treatment of osteoporosis with BPs is still inadequate. Further experimental studies are needed to evaluate the adherence and suggest new treatment options. © 2013 Vieira et al.; licensee BioMed Central Ltd.

Incorporation Of Bisphosphonates In Surface Of The Ti30Ta After Biomimetic Treatment

The purpose of this study was the incorporation of the bisphosphonate (sodium alendronate) in surface of the Ti30Ta alloy after biomimetic treatment. In vitro and in vivo studies were made for to evaluate its incorporation and enhance of the osseointegration.

Treatment of central giant cell lesions using bisphosphonates with intralesional corticosteroid injections

Central giant cell lesions are benign intraosseous proliferative lesions that have considerable local aggressiveness. Nonsurgical treatment methods, such as intralesional corticosteroid injections, systemic calcitonin and interferon have been reported. Recently, bisphosphonates have been used to treat central giant cell lesions. A case of a 36-year-old male with a central giant cell lesion crossing the mandibular midline was treated with intralesional corticosteroids combined with alendronate sodium for the control of systemic bone resorption. The steroid injections and the use of bisphosphonates were stopped after seven months when further needle penetration into the lesion was not possible due to new bone formation. After two years, the bony architecture was near normal, and only minimal radiolucency was present around the root apices of the involved teeth. The patient was followed up for four years, and panoramic radiography showed areas of new bone formation. Thus far, neither recurrence nor side effects of the medication have been detected.

Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude

Background: Homeopathy is based on treatment by similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce 'typical' fractures in patients with osteoporosis, but recent studies report 'atypical' fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism. Method: Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event. Results: Several studies have described multiple cases of 'atypical' low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon. Conclusion: As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this 'unresolved' issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs. Homeopathy (2012) 101, 231-242.