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. Patients and Methods. A retrospective cohort study was conducted involving patients undergoing arthroplasty of the shoulder, at a single institution. Two patients with no previous bisphosphonate treatment were matched to each patient who had received this treatment preoperatively by gender, age, race, ethnicity, body mass index (BMI), and type of arthroplasty. Previous bisphosphonate treatment was defined as treatment occurring during the three-year period before the arthroplasty. The primary outcome measure was the incidence of intraoperative complications and those occurring at one and two years postoperatively. A total of 87 patients were included: 29 in the bisphosphonates-exposed (BP. +. ) group and 58 in the non-exposed (BP. -. ) group. In the BP. +. group, there were 26 female and three male patients, with a mean age of 71.4 years (51 to 87). In the BP. -. group, there were 52 female and six male patients, with a mean age of 72.1 years (53 to 88). Results. Previous treatment with bisphosphonates was positively associated with intraoperative complications (fracture; odds ratio (OR) 39.40, 95% confidence interval (CI) 2.42 to 6305.70) and one-year postoperative complications (OR 7.83, 95% CI 1.11 to 128.82), but did not achieve statistical significance for complications two years postoperatively (OR 3.45, 95% CI 0.65 to 25.28). The power was 63% for complications at one year. Conclusion. Patients who are treated with bisphosphonates during the three-year period before shoulder arthroplasty have a greater risk of intraoperative and one-year postoperative complications compared with those without this previous treatment

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. Patients and Methods. This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded. Results. Interobserver agreement for the PAFF classification was excellent (kappa = 0.944; p < 0.001). On univariate analysis compared with controls, patients with PAFFs had higher mean body mass indices (28.6 kg/m. 2. (. sd. 8.9) vs 21.5 kg/m. 2. (. sd. 3.3); p = 0.009), longer durations of bisphosphonate therapy (median 5.5 years (IQR 3.2 to 10.6) vs 2.4 years (IQR 1.0 to 6.4); p = 0.04), and were less likely to be on alendronate (50% vs 94%; p = 0.02) with an indication of secondary osteoporosis (19% vs 0%; p = 0.049). Duration of bisphosphonate therapy was an independent predictor of PAFF on multivariate analysis (R. 2. = 0.733; p = 0.05). Following primary fracture management, complication rates were higher in PAFFs (9/16, 56%) than controls (5/17, 29%; p = 0.178) with a relative risk of any complication following PAFF of 1.71 (95% confidence interval (CI) 0.77 to 3.8) and of reoperation 2.56 (95% CI 1.3 to 5.2). Conclusion. AFFs do occur in association with prostheses. Longer duration of bisphosphonate therapy is an independent predictor of PAFF. Complication rates are higher following PAFFs compared with typical PFFs, particularly of reoperation and infection. Cite this article: Bone Joint J 2019;101-B:1285–1291

Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where non-impacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth

We performed a retrospective review of all patients admitted to two large University Hospitals in the United Kingdom over a 24-month period from January 2008 to January 2010 to identify the incidence of atypical subtrochanteric and femoral shaft fractures and their relationship to bisphosphonate treatment. Of the 3515 patients with a fracture of the proximal femur, 156 fractures were in the subtrochanteric region. There were 251 femoral shaft fractures. The atypical fracture pattern was seen in 27 patients (7%) with 29 femoral shaft or subtrochanteric fractures. A total of 22 patients with 24 atypical fractures were receiving bisphosphonate treatment at the time of fracture. Prodromal pain was present in nine patients (11 fractures); 11 (50%) of the patients on bisphosphonates suffered 12 spontaneous fractures, and healing of these fractures was delayed in a number of patients. This large dual-centre review has established the incidence of atypical femoral fractures at 7% of the study population, 81% of whom had been on bisphosphonate treatment for a mean of 4.6 years (0.04 to 12.1). This study does not advocate any change in the use of bisphosphonates to prevent fragility fractures but attempts to raise awareness of this possible problem so symptomatic patients will be appropriately investigated. However, more work is required to identify the true extent of this new and possibly increasing problem

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm. -2. (. sd. 7.63) vs 24.65 Nmm. -2. (. sd. 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (. sd. 0.75) vs 4.6 mmAl (. sd. 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). . Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing. Cite this article: Bone Joint J 2013;95-B:1263–8

Aims. Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA). Patients and Methods. In this randomised placebo-controlled, double-blinded trial with 60 participants, we compressed gauze soaked in bisphosphonate solution (ibandronate) or saline against the acetabular bone bed immediately before cementing the acetabular component. RSA, classification of radiolucent lines, the Harris Hip Score (HHS) and the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) were carried out at three-, six-, 12-, and 24-month follow-up. Results. Migration of the cemented acetabular component relative to the pelvis was reduced by movement almost half in the ibandronate group, when measured as maximum total point or as movement of the femoral head (p = 0.001 and 0.004, respectively). Radiolucent lines after one year were classified as absent, partial or complete, and correlated with treatment (rho 0.37; p = 0.004). Only three of 30 patients in the ibandronate group had complete lines, compared with 13 of 28 in the placebo group (p = 0.002). There were no significant effects on HHS or WOMAC score. Conclusion. Considering the power of RSA to predict loosening of cemented acetabular components, and the likelihood that radiolucent lines indicate risk of loosening, these data suggest that local treatment with a bisphosphonate can reduce the risk of late aseptic loosening. Cite this article: Bone Joint J 2017;99-B:317–24

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. Patients and Methods. Between October 2008 and July 2016, 14 patients with failed osteosynthesis of an atypical subtrochanteric femoral fracture were treated with a blade plate (atypical group). Their mean age was 67.8 years (60 to 74); all were female. During the same period, 21 patients with failed osteosynthesis of a typical subtrochanteric fracture underwent restabilization using a blade plate (typical group). Outcome variables included the time of union, postoperative complications, Harris Hip Score, and Sanders functional rating scale. Results. In the atypical group, union was achieved in 12 patients (85.7%) at a mean of 8.4 months (4 to 12). The mean follow-up was 31.2 months (12 to 92) The plate broke in one patient requiring further stabilization with a longer plate and strut-allograft. Another patient with failure of fixation and varus angulation at the fracture site declined further surgery. In the typical group, union was achieved in 18 patients (85.7%) at a mean of 7.9 months (4 to 12). There was no difference in the mean Harris Hip Score between the two groups (83.1 points vs 86.8 points; p = 0.522) at the time of final follow-up. Sanders functional rating scores were good or excellent in 78.6% of the atypical group and in 81.0% of the typical group. Conclusion. The 95° angled blade plate was shown to be an effective fixation modality for nonunion of atypical subtrochanteric fractures with a high rate of union and functional improvement, comparable to those after fractures not associated with bisphosphonate treatment. Cite this article: Bone Joint J 2018;100-B:1511–17

During revision total hip replacement using morcellised compacted bone allograft, 16 patients were randomised to receive a graft which had been rinsed in either an ibandronate solution or in saline. Patients were assessed by dual energy x-ray absorptiometry after operation and at 3, 6, 12 and 24 months. A region of interest between the tip of the femoral stem and the distal plastic plug was chosen to measure the changes in bone density over time. The study was double-blinded. In all the control patients the bone density decreased during the first three months and then remained constant at this lower level. A large proportion of the mass of the bone graft was lost. In contrast, all patients with grafts treated with bisphosphonate showed a slight increase in bone density. The difference between the groups was highly significant at all points in time. We conclude that rinsing the graft in a bisphosphonate solution prevents its resorption and may therefore reduce the risk of mechanical failure. The treatment is simple, inexpensive, and appears virtually free of risk

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. Methods. From January 2003 to January 2016, 305 patients who underwent surgery for AFFs at six hospitals were enrolled. After exclusion, a total of 147 patients were included with a mean age of 71.6 years (48 to 89) and 146 of whom were female. We retrospectively evaluated medical records, and reviewed radiographs to investigate the fracture site, femur bowing angle, presence of delayed union or nonunion, contralateral AFFs, and peri-implant fracture. A statistical analysis was performed to identify the significance of associated factors. Results. The mean follow-up period was 70.2 months (36 to 191). There were 146 AFFs (99.3%) in female patients and the mean age was 71.6 years (48 to 89). The AFFs were located in the subtrochanter and shaft in 52 cases (35.4%) and 95 (64.6%), respectively. The preoperative mean anterior/lateral femoral bowing angles were 10.5° (SD 5.7°)/6.1° (SD 6.2°). The postoperative mean anterior/lateral bowing values were changed by 8.7° (SD 5.4°)/4.6° (SD 5.9°). Bisphosphonates had been used contemporarily in 115 AFFs (78.2%) for a mean of 52.4 months (1 to 204; SD 45.5) preoperatively. Nailing was performed in 133 AFFs (90.5%), and union was obtained at a mean of 23.6 weeks (7 to 85). Delayed union occurred in 41 (27.9%), and nonunion occurred in 13 (8.8%). Contralateral AFF occurred in 79 patients (53.7%), and the use of a bisphosphonate significantly influenced the occurrence of contralateral AFFs (p = 0.019). Peri-implant fractures occurred in a total of 13 patients (8.8%), and a significant increase was observed in cases with plating (p = 0.021) and high grade of postoperative anterolateral bowing (p = 0.044). Conclusion. The use of a bisphosphonate was found to be a risk factor for contralateral AFF, and high-grade postoperative anterolateral bowing and plate fixation significantly increased the occurrence of peri-implant fractures. Long-term follow-up studies on the bilaterality of AFFs and peri-implant fractures are warranted. Cite this article: Bone Joint J 2021;103-B(11):1648–1655

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures. . This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures

In an attempt to increase the life of cementless prostheses, an hydroxyapatite-coated implant which releases a bisphosphonate has been suggested as a drug-delivery system. Our in vitro study was designed to determine the maximum dose to which osteoblasts could be safely exposed. Our findings demonstrated that zoledronate did not impair the proliferation of human osteoblasts when used at concentrations below 1 μ. m. Murine cells can be exposed to concentrations as high as 10 μ. m. . A concentration of 0.01% of titanium particles did not impair the proliferation of either cell line. Zoledronate affected the alkaline phosphatase activity of murine osteoblasts through a chelation phenomenon. The presence of titanium particles strongly decreased the alkaline phosphatase activity of murine osteoblasts. We did not detect any synergic effect of zoledronate and titanium particles on the behaviour of both human and murine osteoblasts

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1. +/−. ) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1. +/−. mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1

Aims

Current levels of hip fracture morbidity contribute greatly to the overall burden on health and social care services. Given the anticipated ageing of the population over the coming decade, there is potential for this burden to increase further, although the exact scale of impact has not been identified in contemporary literature. We therefore set out to predict the future incidence of hip fracture and help inform appropriate service provision to maintain an adequate standard of care.

Management of bisphosphonate-associated subtrochanteric fractures remains opinion- or consensus-based. There are limited data regarding the outcomes of this fracture.

We retrospectively reviewed 33 consecutive female patients with a mean age of 67.5 years (47 to 91) who were treated surgically between May 2004 and October 2009. The mean follow-up was 21.7 months (0 to 53). Medical records and radiographs were reviewed to determine the post-operative ambulatory status, time to clinical and radiological union and post-fixation complications such as implant failure and need for second surgery.

The predominant fixation method was with an extramedullary device in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation or no weight-bearing initially. The mean time to full weight-bearing was 7.1 months (2.2 to 29.7). The mean time for fracture site pain to cease was 6.2 months (1.2 to 17.1). The mean time to radiological union was 10.0 months (2.2 to 27.5). Implant failure was seen in seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9). Revision surgery was required in ten patients (33%, 95 CI 19.2 to 51.2).

A large proportion of the patients required revision surgery and suffered implant failure. This fracture is associated with slow healing and prolonged post-operative immobility.

Cite this article: Bone Joint J 2014;96-B:658–64.

Total knee arthroplasty (TKA) is known to lead to a reduction in periprosthetic bone mineral density (BMD). In theory, this may lead to migration, instability and aseptic loosening of the prosthetic components. Bisphosphonates inhibit bone resorption and may reduce this loss in BMD. We hypothesised that treatment with bisphosphonates and calcium would lead to improved BMD and clinical outcomes compared with treatment with calcium supplementation alone following TKA. A total of 26 patients, (nine male and 17 female, mean age 67 years) were prospectively randomised into two study groups: alendronate and calcium (bisphosphonate group, n = 14) or calcium only (control group, n = 12). Dual energy X-ray absorptiometry (DEXA) measurements were performed post-operatively, and at three months, six months, one, two, four, and seven years post-operatively. . Mean femoral metaphyseal BMD was significantly higher in the bisphosphonate group compared with controls, up to four years following surgery in some areas of the femur (p = 0.045). BMD was observed to increase in the lateral tibial metaphysis in the bisphosphonate group until seven years (p = 0.002), and was significantly higher than that observed in the control group throughout (p = 0.024). There were no significant differences between the groups in the central femoral metaphyseal, tibial medial metaphyseal or diaphyseal regions of interest (ROI) of either the femur or tibia. Bisphosphonate treatment after TKA may be of benefit for patients with poor bone quality. However, further studies with a larger number of patients are necessary to assess whether this is clinically beneficial. Cite this article: Bone Joint J 2015;97-B:337–45

Aims. Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. Patients and Methods. The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants’ discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. Results. Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. Conclusion. These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402–1407

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

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites

We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N vs 81 N; bone volume density 19% vs 20%). Treatment with PTH for two weeks followed by pamidronate almost doubled the pull-out force (152 N; p < 0.001) and the bone volume density (37%; ANOVA, p < 0.001). Pamidronate alone did not have this effect (89 N and 25%, respectively). Thus, the deterioration can be blocked by bisphosphonates. The clinical implications are discussed

Aims. The Fassier Duval (FD) rod is a third-generation telescopic implant for children with osteogenesis imperfecta (OI). Threaded fixation enables proximal insertion without opening the knee or ankle joint. We have reviewed our combined two-centre experience with this implant. Methods. In total, 34 children with a mean age of five years (1 to 14) with severe OI have undergone rodding of 72 lower limb long bones (27 tibial, 45 femoral) for recurrent fractures with progressive deformity despite optimized bone health and bisphosphonate therapy. Data were collected prospectively, with 1.5 to 11 years follow-up. Results. A total of 24 patients (33%) required exchange of implants (14 femora and ten tibiae) including 11 rods bending with refracture. Four (5%) required reoperation with implant retention. Loss of proximal fixation in the femur and distal fixation in the tibia were common. Four patients developed coxa vara requiring surgical correction. In total, 13 patients experienced further fractures without rod bending; eight required implant revision. There was one deep infection. The five-year survival rate, with rod revision as the endpoint, was 63% (95% confidence interval (CI) 44% to 77%) for femoral rods, with a mean age at implantation of 4.8 years (1.3 to 14.8), and 64% (95% CI 36% to 82%) for tibial rods, with a mean age at implantation of 5.2 years (2.0 to 13.8). Conclusion. FD rods are easier to implant but do not improve on the revision rates reported for second generation T-piece rods. Proximal femoral fixation is problematic in younger children with a partially ossified greater trochanter. Distal tibial fixation typically fails after two years. Future generation implants should address proximal femoral and distal tibial fixation to avoid the majority of complications in this series. Cite this article: Bone Joint J 2020;102-B(8):1048–1055

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

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

An atypical femoral fracture (AFF), with a transverse fracture radiologically through the lateral cortex is a rare but serious condition. In order to improve our ability to identify patients with this condition, we retrospectively surveyed all subtrochanteric, peri-implant and diaphyseal femoral fractures in patients aged ≥ 65 years who underwent surgical treatment at our hospital between 2004 and 2011. We describe the incidence of atypical fractures and their characteristics, with observational data including a review of the hospital and general practitioner records. Clinical outcomes were evaluated using the Harris hip score (HHS) and the timed up-and-go (TUG) test. Atypical fractures only occurred in women with an incidence of 9.8 per 100 000 person-years. The incidence in those who were treated with bisphosphonates was 79.0 per 100 000 person-years; eight of 17 fractures occurred around metal implants. There was a high incidence of delayed union and revision surgery. A total of nine patients (ten AFFs) were available for review at a mean follow-up of 36.5 months (10 to 104). The clinical outcome was poor with a mean HHS of 58.9 (95% CI 47.4 to 70.4) and a mean TUG test of 25.7 s (95% CI 12.7 to 38.8). The delay in diagnosis and treatment of AFF may result from a lack of knowledge of this condition. Cite this article: Bone Joint J 2014; 96-B:1035–40

Cancer-induced bone diseases are often associated with increased bone resorption and pathological fractures. In recent years, osteoprotective agents such as bisphosphonates have been studied extensively and have been shown to inhibit cancer-related bone resorption in experimental and clinical studies. The third-generation bisphosphonate, ibandronate (BM 21.0955), is a potent compound for controlling tumour osteolysis and hypercalcaemia in rats bearing Walker 256 carcinosarcoma. We have studied the effect of ibandronate given as an interventional treatment on bone strength and bone loss after the onset of tumour growth in bone. Our results suggest that it is capable of preserving bone quality in rats bearing Walker 256 carcinosarcoma cells. Since other bisphosphonates have produced comparable results in man after their success in the Walker 256 animal models our findings suggest that ibandronate may be a powerful treatment for maintaining skeletal integrity in patients with metastatic bone disease

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA

An 81-year-old woman presented with a fracture in the left femur. She had well-fixed bilateral hip replacements and had received long-term bisphosphonate treatment. Prolonged bisphosphonate use has been recently linked with atypical subtrochanteric and diaphyseal femoral fractures. While the current definition of an atypical fracture of the femur excludes peri-prosthetic fractures, this case suggests that they do occur and should be considered in patients with severe osteopenia. Union of the fracture followed cessation of bisphosphonates and treatment with teriparatide. Thus, this case calls into question whether prophylactic intramedullary nailing is sufficient alone to treat early or completed atypical femoral fractures

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone

The use of bisphosphonates in the treatment of avascular necrosis of the femoral head is an encouraging but relatively new option with most published data being derived from small trials with limited follow-up. We present a clinicoradiological analysis of 395 hips with avascular necrosis which were treated with oral alendronate for three years with a mean follow-up of four years (1 to 8). Our results show an improvement in the clinical function, a reduction in the rate of collapse and a decrease in the requirement for total hip replacement, compared with the findings of other studies in which no treatment was given. This improvement is particularly marked if the treatment is begun in the pre-collapse stages of the disease. Even in Ficat stage-III hips some benefit was obtained from treatment with alendronate by at least a delay in the need for total hip replacement

Aims

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas.

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction. After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm. 3. over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae. The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis

We investigated the fracture-free survival of long bones stabilised by a telescopic intramedullary rod (TIMR) in patients with osteogenesis imperfecta with respect to the remodelling status of fracture or osteotomy sites and TIMR regions, in order to identify risk factors for fracture. A total of 44 femora and 28 tibiae in 25 patients with a mean age of 5.0 years (1.9 to 10.5) at presentation were studied. There were six patients with Sillence type I, five with type III, 13 with type IV and one with type V osteogenesis imperfecta. All received bisphosphonate treatment at the same stage during the mean follow-up of 7.3 years (0.5 to 18.1). The fracture-free survival was estimated at 6.2 years (95% confidence interval 5.1 to 7.3) by Kaplan-Meier analysis. More than half the fracture or osteotomy sites remained in a less-remodelled state at the latest follow-up or time of fracture. Of the 33 fractures, 29 (87.9%) occurred in long bones containing a less-remodelled site, and these fractures were located at this site. The relative fracture risk at the rod tip was significantly greater than in any other TIMR region (p < 0.001), and this was higher in bone segments having a less-remodelled site. This study shows a persistent fracture risk in TIMR-stabilised long bones, especially at less-remodelled fracture or osteotomy sites and at the rod tip

Aims

Perthes' disease (PD) is a relatively rare syndrome of idiopathic osteonecrosis of the proximal femoral epiphysis. Treatment for Perthes' disease is controversial due to the many options available, with no clear superiority of one treatment over another. Despite having few evidence-based approaches, many patients with Perthes' disease are managed surgically. Positive outcome reporting, defined as reporting a study variable producing statistically significant positive (beneficial) results, is a phenomenon that can be considered a proxy for the strength of science. This study aims to conduct a systematic literature review with the hypothesis that positive outcome reporting is frequent in studies on the treatment of Perthes' disease.

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We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone.

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We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton.

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To determine if patient ethnicity among patients with a hip fracture influences the type of fracture, surgical care, and outcome.

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Periprosthetic fractures (PPFs) around the knee are challenging injuries. This study aims to describe the characteristics of knee PPFs and the impact of patient demographics, fracture types, and management modalities on in-hospital mortality.

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This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults.

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment

The Gorham-Stout Syndrome (Gorham’s massive osteolysis) is a rare condition in which spontaneous, progressive resorption of bone occurs. The aetiology is poorly understood. We report six cases of the condition and present evidence that osteolysis is due to an increased number of stimulated osteoclasts. This suggests that early potent antiresorptive therapy such as with calcitonin or bisphosphonates may prevent local progressive osteolysis

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Debate continues regarding the optimum management of periprosthetic distal femoral fractures (PDFFs). This study aims to determine which operative treatment is associated with the lowest perioperative morbidity and mortality when treating low (Su type II and III) PDFFs comparing lateral locking plate fixation (LLP-ORIF) or distal femoral arthroplasty (DFA).

Periprosthetic bone loss after total joint arthroplasty is a major clinical problem resulting in aseptic loosening of the implant. Among many cell types, osteoblasts play a crucial role in the development of peri-implant osteolysis. In this study, we tested the effects of calcitriol (1α,25-dihydroxy-vitamin-D. 3. ) and the bisphosphonate pamidronate on titanium-particle- and TNF-α-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. We monitored the expression of procollagen α1[1], osteocalcin, osteonectin and alkaline phosphatase mRNAs by Northern blots and real-time reverse transcription and polymerase chain reaction analyses. The release of various cytokines was also analysed by ELISA. We found that calcitriol or pamidronate could only partially recover the altered functions of osteoblasts when added alone. Only a combination of these compounds restored all the tested functions of osteoblasts. The local delivery of these drugs may have therapeutic potential to prevent or to treat periprosthetic osteolysis and aseptic loosening of implants

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Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up.

We examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits. Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm. 2. ) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p< 0.05). Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate. Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate

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There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?

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Hip fractures in patients < 60 years old currently account for only 3% to 4% of all hip fractures in England, but this proportion is increasing. Little is known about the longer-term patient-reported outcomes in this potentially more active population. The primary aim is to examine patient-reported outcomes following isolated hip fracture in patients aged < 60 years. The secondary aim is to determine an association between outcomes and different types of fracture pattern and/or treatment implants.

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To compare the cost-utility of standard dressing with incisional negative-pressure wound therapy (iNPWT) in adults with closed surgical wounds associated with major trauma to the lower limbs.

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Heterotopic ossification (HO) is a potentially devastating complication of the surgical treatment of a proximal humeral fracture. The literature on the rate and risk factors for the development of HO under these circumstances is lacking. The aim of this study was to determine the incidence and risk factors for the development of HO in these patients.