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Osteoporosis is an asymptomatic disease characterized by bone weakening and predisposition to fragility (insufficiency) fractures and can have devastating effects on individual life and great financial impact on the economy. Bisphosphonates are used worldwide for the primary and secondary prevention of osteoporotic fractures. However, increasing ev...
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Introduction:
The mai...
Citations
... We found seven papers that report on the use of denosumab after an AFF in 10 patients (18,45,58,(68)(69)(70)(71). Seven patients switched from bisphosphonates to denosumab just before or after the first AFF. ...
... (63), mean duration of bisphosphonates (n=3) (55), median no. of denosumab doses (n=3) (55). Included articles: (8,42,(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68) A c c e p t e d M a n u s c r i p t 35 ...
Context
Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
Evidence acquisition
We performed a systematic review to evaluate effects of teriparatide, raloxifene and denosumab on healing and occurrence of AFF.
Evidence synthesis
We retrieved 910 references and reviewed 67 papers, including 31 case reports, nine retrospective and three prospective studies on teriparatide. There were no randomized controlled trials. We pooled data on fracture union (n=98 AFFs on teriparatide) and found that radiological healing occurred within six months of teriparatide in 13 of 30 conservatively managed incomplete AFFs (43%), nine of 10 incomplete AFFs with surgical intervention (90%) and 44 of 58 complete AFFs (75%). In nine of 30 non-operated incomplete AFFs (30%) no union was achieved after 12 months and four fractures (13%) became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and eight without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in one patient and two cases of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including one bisphosphonate-naïve patient.
Conclusions
There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.
... The duration of bisphosphonate treatment ranged from 0.04 to 20 years. Concomitant glucocorticoid use could be assessed in 272 patients, 20,21,24,26,28,30,31,33,36,37,40,41,44,46,48,50,51,[54][55][56][57][60][61][62][63][64][65][66][67][68][69][70][71][72]74,75,77,79,80,86,[88][89][90][91][92][93][94] and was given to 49 patients (18%). Complete fracture. ...
Aims:
Treatment guidelines for atypical femoral fractures associated with bisphosphonates have not been established. We conducted a systematic review of the treatment of atypical femoral fractures first, to evaluate the outcomes of surgical fixation of complete atypical fractures and secondly, to assess whether prophylactic surgery is necessary for incomplete atypical fractures.
Materials and methods:
Case reports and series were identified from the PubMed database and were included if they described the treatment of atypical femoral fractures. In total, 77 publications met our inclusion criteria and 733 patients with 834 atypical complete or incomplete femoral fractures were identified.
Results:
For complete fractures, internal fixation was predominantly achieved by intramedullary nailing. The mean time to healing post-operatively was 7.3 months (2 to 31). Revision surgery for nonunion or implant failure was needed in 77 fractures (12.6%). A greater percentage of fractures treated with plate fixation (31.3%) required revision surgery than those treated with intramedullary nailing (12.9%) (p < 0.01). Non-operative treatment of incomplete fractures failed and surgery was eventually needed in nearly half of the patients (47%), whereas prophylactic surgery was successful and achieved a 97% rate of healing.
Conclusion:
Intramedullary nailing is the first-line treatment for a complete fracture, although the risk of delayed healing and revision surgery seems to be higher than with a typical femoral fracture. Non-operative treatment does not appear to be a reliable way of treating an incomplete fracture: prophylactic intramedullary nailing should be considered if the patient is in intractable pain. Radiographs of the opposite side should be obtained routinely looking for an asymptomatic fracture. Bisphosphonates must be discontinued but ongoing metabolic management in the form of calcium and/or vitamin D supplements is advisable. Teriparatide therapy can be considered as an alternative treatment. Cite this article: Bone Joint J 2017;99-B:295-302.
... Now, with the 4-year results at hand, we no longer believe this. With the reported occasional occurrence of atypical subtrochanteric or diaphyseal femoral fracture in patients with long-term use of alendronate (Sellmeyer 2010) and risedronate (Alfahad et al. 2012), the risk outweighs the merits of treatment in our opinion. ...
Background and purpose
We have previously shown that during the first 2 years after total hip arthroplasty (THA), periprosthetic bone resorption can be prevented by 6 months of risedronate therapy. This follow-up study investigated this effect at 4 years.
Patients and methods
A single-center, double-blind, randomized placebo-controlled trial was carried out from 2006 to 2010 in 73 patients with osteoarthritis of the hip who were scheduled to undergo THA. The patients were randomly assigned to receive either 35 mg risedronate or placebo orally, once a week, for 6 months postoperatively. The primary outcome was the percentage change in bone mineral density (BMD) in Gruen zones 1 and 7 in the proximal part of the femur at follow-up. Secondary outcomes included migration of the femoral stem and clinical outcome scores.
Results
61 of the 73 patients participated in this 4-year (3.9- to 4.1-year) follow-up study. BMD was similar in the risedronate group (n = 30) and the placebo group (n = 31). The mean difference was −1.8% in zone 1 and 0.5% in zone 7. Migration of the femoral stem, the clinical outcome, and the frequency of adverse events were similar in the 2 groups.
Interpretation
Although risedronate prevents periprosthetic bone loss postoperatively, a decrease in periprosthetic BMD accelerates when therapy is discontinued, and no effect is seen at 4 years. We do not recommend the use of risedronate following THA for osteoarthritis of the hip.
Background
Although bone scan might be useful to detect incomplete atypical femoral fractures (AFFs) earlier than radiographs, there is no study on predicting further progression to a complete fracture among incomplete AFFs. Our purposes are to determine whether bone scan detects impending complete fracture among incomplete AFFs.
Methods
We reviewed 18 patients (20 AFFs) who underwent bone scan at the diagnosis of incomplete AFF and were not treated with prophylactic fixation. A diagnosis of impending complete fracture was made, when the femur completely fractured within 6 months after the scan. We correlated radioisotope uptake with the impending complete fracture to calculate sensitivity, specificity, positive predictive value and negative predictive value of bone scan.
Results
Thirteen AFFs (65%, 13/20) showed a positive uptake in bone scan. Among the 13, only one femur was completely fractured within 6 months. None of the 7 femurs without uptake in bone scan fractured. In diagnosing impending complete fracture, the sensitivity of bone scan was 100% and negative predictive value was 100%. However, the specificity (36.8%) and positive predictive value (7.7%) were quite low.
Conclusion
Bone scan has no significant role in detecting the impending complete fracture, and a positive uptake does not mean the necessity of prophylactic fixation of incomplete AFF.
There are a number of case reports about women undergoing long-term bisphosphonate therapy who have suffered an atypical subtrochanteric or femoral shaft fracture due to an inadequate trauma. The present case reports on a patient who underwent a subtrochanteric femur fracture with the inserted AO femur interlocking nail.
Atypical femoral fractures (AFFs) were first recognized as unusual non-fragility stress fractures happening in elderly patients at unexpected locations in the femur. Later studies associated these AFFs with long-term use of bisphosphonates and other antiresorptive agents. A task force organized by the American Society for Bone and Mineral Research developed a case definition for AFF identification. Here, we summarize the task force recommendations, indicate the material and geometric properties of bones that are common to AFFs, identify mechanical and bone quality parameters that may be associated with AFFs, summarize potential mechanisms for these fractures, and briefly review clinical strategies to eliminate this relatively rare but important complication of treatment associated with antiresorptive agents.
Bisphosphonates are extensively used to treat bone metabolism disorders; meanwhile, these drugs have important side effects such as jaw osteonecrosis and femoral fracture. Therefore, studies have been conducted aimed at better understanding their mechanism of action and determining a course of action to avoid these side effects. We present here a literature review focusing on the laboratory methods available for investigating bisphosphonate effects on body tissues. There are many different methods available for this purpose, but the appropriate application of these methods and knowledge of their limitations are crucial for understanding the effects of bisphosphonates.
