Introduction and Aims: This study evaluates the effect of risedronate (Actonel) on proximal femoral bone loss after total hip arthroplasty (THA). Studies have shown that alendronate (Fosamax) reduces periprosthetic bone loss after primary THA. We hypothesise that patients who take risedronate, post-THA, will have less bone loss than patients not taking risedronate. Method: All patients in this prospective study undergo uncemented THA and follow the same post-operative protocol. Patients in the study group take five mg of risedronate daily, beginning five to seven days pre-operatively, and continuing for 24 months after surgery. Patients randomised to the control group do not receive risedronate. Dual energy x-ray absorptiometry (DEXA) scans of the operated proximal femur are performed on all patients pre-operatively, three to seven days post-operatively, and then six weeks, six months, one year and two years post-operatively. Longitudinal changes in bone mineral density (BMD) are compared within and between the two groups. Results: Analysis of data for female subjects showed the percent change in BMD (g/cm. 2. ) for the control group at six months was −9.71% and for the study group −4.55%. Longitudinal changes in BMD between groups were examined using repeated measures analysis within each gender and were found to be significantly different between groups of females (p=.05). A similar trend was observed among the male subjects. One and two-year prospective data will be presented at the meeting. Conclusion: Bone loss after THA can increase the rate of failure of THA and cause revision surgery to be more complex and have compromised outcomes. Short-term data reveal significantly decreased bone loss after uncemented THA among patients taking risedronate

The treatment of fracture accompanied with bone defect remains a challenge in skeletal surgery. For bone defect, we have to give a material to support healing process. Some material is allograft given at second to sixth weeks to avoid osteoclastic activity. We try to give primary allograft and to prevent osteoclastic activity we use risedronat. Risedronate (Actonel(r)) is one of bisphosphonate group that decrease the turnover of the bone by activating apoptosis of osteoclast and increasing osteoblast activity. The aim of this paper is to evaluate radiologically and histologically result for the effect of the bone healing process for a fracture associated with bone defect which treated by a combination of fresh frozen allograft and risedronate (Actonel(r)). The design is an experimental study, Post Test Only Control Group Design, using adult male white rats spraque-dawley. Right open tibial osteotomies to create bone defect are performed surgically and put Kirschner wire as intramedularry fixation. Rats are divided into four groups, with six samples in each group. Group one with bone defect in 2 mm, group two with bone defect 2 mm and put fresh frozen allograft, group three with bone defect 2 mm and put fresh frozen allograft and given Actonel(r) 350g a week for two first week, and group four with bone defect 2 mm and put fresh frozen allograft and given Actonel(r) 350g a week for six week. Six weeks after implantation, the animals were sacrificed, and the tibia were evaluated by radiological and histological studies. Radiologically, there are significant different of relative bone healing result between ungiven risedronat group (group one and two) and given risedronat group (group three and four) (Kolmogorof smirnov test). Histological results by one way anova shows varians test was p = 0,168 (p > 0,05). Anova test was p = 0,000 (p < 0,05), post hoc Turkey HSD there was not significant different between group one and group two p = 0,969, between group one dan group four p = 0,634 (p > 0,05), between group two dan group four p = 0,634 (p > 0,05); a significant different between group one and group three p = p = 0,000 (p<0,05) between group two and group three p = 0,01 (p < 0,05), and group three and group four p=0,004 (p < 0,05). Risedronate (Actonel(r)) influence the healing process of two mm bone defect radiologically. By histologically, two first weeks given of risedronate at group three have a better result than groups one, two and four

This prospective multicentre study was undertaken to determine whether the timing of the post-operative administration of bisphosphonate affects fracture healing and the rate of complication following an intertrochanteric fracture. Between August 2008 and December 2009, 90 patients with an intertrochanteric fracture who underwent internal fixation were randomised to three groups according to the timing of the commencement of risedronate treatment after surgery: Group A (from one week after surgery), Group B (from one month after surgery), and Group C (from three months after surgery). The radiological time to fracture healing was assessed as the primary endpoint, and the incidence of complications, including excessive displacement or any complication requiring revision surgery, as the secondary endpoint. The mean time to fracture healing post-operatively in groups A, B and C was 10.7 weeks (. sd. 4.4), 12.9 weeks (. sd. 6.2) and 12.3 weeks (. sd. 7.1), respectively (p = 0.420). At 24 weeks after surgery, all fractures had united, except six that had a loss of fixation. Functional outcomes at one year after surgery according to the Koval classification (p = 0.948) and the incidence of complications (p = 0.386) were similar in the three groups. This study demonstrates that the timing of the post-operative administration of bisphosphonates does not appear to affect the rate of healing of an intertrochanteric fracture or the incidence of complications

Aims

The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip.

Aims

This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

Purpose. In 2010, the new clinical guideline of Osteoporosis Canada for the diagnosis of osteoporosis, clearly indicates that patients with high-risk of fracture are those that have already sustained a fracture (osteoporotic fracture). Until now, only 12% of the 3,400 fractures that we treat each year receive a treatment for osteoporosis. We are validating an evaluation protocol and a multidisciplinary systematic follow-up approach for osteoporosis. Patients are managed by a clinical nurse specialist. We are recruiting 543 patients with an osteoporotic fracture at Hal du Sacré-Coeur de Montréal. We aim to evaluate: 1) the incidence of a second osteoporotic fracture, 2) the initiation of a treatment and determine the compliance and adherence to treatment and 3) the evaluation of CTX-1 and Osteocalcin at Baseline, 6, 12,18 et 24 months (treatment efficacy) and 4) the functional outcome and quality of life post-fracture. Method. We've enrolled 153 subjects (men and women) over 40 years of age who were treated for an osteoporotic fracture at the orthopaedic clinic of Hal du Sacré-Coeur de Montréal. After starting a treatment protocol for osteoporosis, the subjects will be followed for a 24 months period at different time intervals. During these visits, they fill up functional outcome questionnaires, undergo physical exam, blood test, x rays and their compliance to treatment is evaluated. Results. Mean patients age was 65 y.o (+ 13). Two hundred seventeen patients were approached and 153 patients were enrolled (23 men and 130 women). Eleven patients refused to be part of the systematic follow up because they were satisfied with their family doctors osteoporosis management. Fifty-three were explained treatment and follow up and refused to participate. Thirteen patients (9%) dropped out after six months. One patient died. Twenty-one patients (13.7%) were already on bisphosphonates and 53 pts (34.6 %) had already sustained a fragility fracture. All patients were prescribed risedronate except three that were prescribed zoledronic acid or pamidronate for intolerance or contraindication to oral bisphosphonates. Up to now, we obtained 71% adherence and 91% persistence. After validation, 10% of the patients needed to be referred to a rheumatologist and 90% of the patients were managed by the clinical nurse specialist. Conclusion. Our multidisciplinary systematic follow up of osteoporotic fracture improved the osteoporosis treatment rate from 12 to 71 % in our orthopaedic surgery department. Clinical Nurse Specialists could represent the best approach to manage the underlying osteoporosis that leads to fragility fractures

Aims

The aim of this study was to compare the cost-effectiveness of surgical fixation with Kirschner (K-)wire ersus moulded casting after manipulation of a fracture of the distal radius in an operating theatre setting.

Emerging evidence has linked the long-term use of alendronate (fosamax) with subtrochanteric insufficiency fractures. However, findings to date have been anecdotal. The aims of this study were to determine the incidence of subtrochanteric insufficiency fractures and identify whether they were more prevalent following the introduction of alendronate in Australia. All patients that presented between January 2007 and February 2009 with low- energy subtrochanteric fracture were identified. Similar data were collected between January 1995 and February 1997 as this was immediately prior to introduction of alendronate in Australia. The radiographs were examined for failure due to pre- existing insufficiency fracture. Characteristic findings were a transverse fracture line on the tension side of the femur with lateral cortical thickening immediately adjacent to the fracture. Relevant details from the history were recorded. We also separately identified all patients that presented between 2007 and 2009 with a proximal femoral fracture and determined the proportion taking alendronate. One hundred and seventeen patients with low-energy subtrochanteric fracture were included. Seventy-nine patients presented between 2007 and 2009 and 38 presented between 1995 and 1997. Forty-one of the 79 (52%) patients were identified as having radiograph findings suggestive of underlying insufficiency fracture, whilst none were identified prior to the introduction of alendronate. Of the 41 patients with subtrochanteric insufficiency fracture, 40 (98%) had been taking alendronate and one had been taking risedronate. Twenty-nine of the 41 (71%) complained of prodromal pain in the affected femur. Eighteen of the 41 (44%) demonstrated subtrochanteric insufficiency changes on the contralateral side and 9 of 41 (22%) sustained spontaneous non-traumatic fracture during activities of daily living. Of the 38 patients without insufficiency changes, 12 (32%) had been taking alendronate. Alendronate use was therefore strongly suggestive of insufficiency fracture (sensitivity = 98%, specificity = 84%, PPV = 77%, NPV = 99%, LR+ = 6). The mean duration of alendronate use in those with insufficiency fracture was 7.1 years (95% CI, 6.6-7.6 years). The mean duration in those without was 3.2 years (95% CI, 2.6-3.8 years, P<0.0001). Three hundred and ninety eight patients presented with a low-energy proximal femur fracture between 2007 and 2009. Of these, only 52 (13%, P<0.0001) were taking alendronate. This is the largest study in the literature on subtrochanteric insufficiency fractures and alendronate therapy. Confirming recent reports, alendronate use was strongly suggestive of subtrochanteric insufficiency fracture. Our findings provide the most compelling evidence to date of the potential long-term sequelae of alendronate but more research is needed before definitive conclusions can be made

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

The risk of further fractures increases 2–10 times after the first fracture. Actual fracture risk for the given person (absolute fracture risk) can be calculated from data collected in 10-year prospective studies (NHANES or Kanis 2001). To calculate absolute fracture risk one has to multiply age-related risk factor ascertained in above studies by the coefficient estimated for particular factors influencing possible fracture (relative fracture risk). The most commonly used factors are: age (RR 2.0 for each 5 yrs over 65), low BMD (RR/SD 1.4–2.6), low-energy fracture after the age of 40 (RR 4.0), proximal femur fracture in mother (*RR 1.9), body mass lower than 58 kg (*RR 1.9), early menopause – before the age of 45, smoking (RR 1.2), susceptibility to falls (*RR 3.5), corticosteroids intake. Absolute fracture risk in 60-year-old woman whose foreseen 10-year probability of femoral neck fracture is 2.3% with normal BMD but burden by factors marked by asterisks would be: 2.3% x 1.9 x 1.9 x 3.5 = 29%. As 76% of fractures occur in women with normal BMD absolute fracture risk is the most objective information. In case of proximal femoral fracture 10-year probability of 10% or more fracture risk provides a cost effective threshold for women in Sweden. We can increase bone mineral density by pharmacological intervention. Every patient should be given calcium and vit. D supplementation and a specific medication, which should be adjusted to: age, sex and presence of hot flashes and fractures. HRT is preferred in women aged 50–60 yrs suffering from hot flashes. HRT decreases the risk of spine (50%) and proximal femur fracture (40%). However some risk of breast and uterine cancer has to be taken into consideration. Selective estrogen modulators (SERM; raloxifene) act as estrogen agonists on bone and cardiovascular system but as antagonists on breast tissue. Decrease of spinal fracture (45%) and breast cancer incidence (70%) is proven but no positive action on proximal femur is reported. In women who underwent osteoporotic fracture one can apply bisphosphonates, strontium ranelate or PTH. Alendronate reduces spine fractures (47%) and proximal femur fractures (51%). Similar effects are documented for risedronate (spine – 60% and proximal femur 40–56%). Strontium ranelate not only inhibits bone resorption but also stimulates bone formation. Decrease of spine and proximal femur fractures occurrence has been proven (41%). PTH injected sc. in daily doses is the most powerful compound which rebuilds bone trabeculae in severe cases and reduces incidence of peripheral fractures (53%). Calcitonin is effective in spine fractures but not in proximal femur. Fall prevention program should be implemented in all patients with osteoporosis independently from pharmacological intervention

Aims

The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years.

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Objectives

Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.

Aims

Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment.

Aims

The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes.

Aims

The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment.

Objectives

Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA.

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs.

We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice.

Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib.

Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage.

Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease.

Cite this article: Bone Joint J 2016;98-B:160–5.