Background
Total hip arthroplasty (THA) has become a popular and successful surgical option for patients with hip osteoarthritis or hip fracture [
1]. Some studies revealed that more than 75% of the revision arthroplasties were performed due to prosthesis loosening and peri-prosthetic fracture, which were accompanied by severe periprosthetic bone loss [
2]. If an ideal drug suppressing the bone resorption after THA was found, the service life of prosthesis would be much prolonged [
3,
4].
Numerous studies have focused on peri-prosthetic bone metabolism after THA [
5,
6]. Bone resorption is considered to be the main reason for prosthesis loosening [
7]. Currently, bisphosphonates are anti-resorptive agents which promote bone mineralization and inhibit the biological effect of osteoclasts [
8]. Many RCTs have demonstrated its beneficial effect on preserving periprosthetic bone in cementless THA [
9,
10]. The risedronate has been used successfully to prevent osteoporotic fractures, mainly in the hip and vertebrae, by inhibiting osteoclast activity [
11]. Risedronate can also reduce the risk of vertebral and hip fractures in patients with osteoporosis [
12]. It could rapidly reduce bone turnover rates in adult patients at high risk of fractures [
13]. In addition, risedronate has the potential efficacy in protecting against osteoporotic fractures and improving periprosthetic bone quality. Regardless of the potential efficacies of risedronate, no approved therapy for BMD loss associated with THA has been achieved due to the low evidence level of current articles.
Due to the potential positive effects, risedronate has been recommended to be used in THA as routine. However, there is less scientific evidence on the use of risedronate in preventing periprosthetic bone loss in THA. Thus, the purpose of this meta-analysis from RCTs was to evaluate whether oral risedronate could reduce femoral periprosthetic BMD loss and also increase the hip function in patients undergoing primary THA.
Methods
This meta-analysis was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
Search strategy
We systematically searched papers in the following databases: PubMed, Embase, Web of Science, Cochrane Library, and Chinese Wanfang database. The following keywords were used in combination with Boolean operators AND or OR: “total hip replacement OR total hip arthroplasty” OR “THA” OR “THR” OR ““Arthroplasty, Replacement, Hip”[Mesh]” AND “risedronate.” No restrictions were imposed on language. The references of the relevant reviews were also reviewed to identify additional articles. All analyses were based on previous published studies; thus, no ethical approval and patient consent are required.
Inclusion and exclusion criteria
Inclusion criteria
1.
Participants: RCTs enrolling adult patients undergoing THA.
2.
Interventions: Experimental groups received oral risedronate.
3.
Comparisons: Control groups received equivalent placebo or no treatment.
4.
Outcomes: Change in bone mineral density (BMD) in Gruen zones [
14] and the Harris hip scores.
5.
Study design: RCTs were considered as potentially relevant included articles in our study.
Exclusion criteria
Studies were excluded as follows: revision THA, patients suffer from an allergy to the risedronate, non-RCTs, letter, or without included outcomes.
Selection criteria
Two reviewers independently reviewed the abstracts of the potential articles identified by the above searches. Subsequently, the full text of the studies that met the inclusion criteria were screened, and a final decision was made by discussion. A senior author had the final decision in any case of disagreement regarding which studies to be included.
Two of the authors independently extracted data from the included studies. Corresponding authors were consulted for details of incomplete data. The following data were extracted and recorded in a spreadsheet: first author, publication year, sample size, baseline characteristics, intervention procedures, outcome, and duration of the follow-up. Other relevant data were also extracted from individual studies. Primary outcomes were changes in BMD in Gruen zones 1 and 7. Secondary outcomes were changes in BMD in Gruen zone 2, 3, 4, 5, and 6 and the Harris hip scores.
Outcome measures and statistical analyses
The main outcomes were the changes in BMD in Gruen zones and the Harris hip scores. Continuous outcomes (Changes in BMD in Gruen zones and the Harris hip scores) were expressed as the weighted mean difference (WMD) and 95% confidence interval (CI). Statistical significance was set at P < 0.05 across the trials. Stata 12.0 (Stata Corp., College Station, TX) was used for the meta-analysis. Statistical heterogeneity was tested using I2 statistic. As the doses of risedronate were different, a random-effect model was chosen to avoid heterogeneity. Publication bias was not tested because the number of included studies was less than ten.
Discussion
This is the first meta-analysis comparing the efficacy of oral risedronate in reducing bone loss after THA. Results indicated that oral risedronate can significantly increase the BMD around uncemented femoral stem (Gruen zone 1). There was little clinical significance between the risedronate and control groups in the Gruen zones 2, 3, and 7. Oral risedronate can also increase the Harris hip scores and thus has a positive role in improving the postoperative outcomes of the hip.
Our study was uniquely undertaken using the following approaches: (1) we systematically searched the electronic databases and calculated all of the outcomes with random-effect model, (2) our meta-analysis was performed and analyzed in accordance with the best practice methods recommended by the Cochrane Collaboration [
17], and (3) only focused on the risedronate for bone loss after THA and thus avoid the clinical heterogeneity. In 2011, Prieto-Alhambra et al. [
18] conducted a population-based parallel-cohort trial and indicated that bisphosphonates reduced the fracture risk among THA patients (hazard ratio (HR) = 0.56, 95% CI 0.38–0.82). We assessed the BMD around uncemented femoral stem (Gruen zones 1, 2, 3, 4, 5, 6, and 7). Final results indicated that oral risedronate had a positive role in increasing the BMD around uncemented femoral stem (Gruen zones 1, 2, 3, and 7). There was no significant difference between the BMD around uncemented femoral stem (Gruen zones 4, 5, and 6).
From a previous meta-analysis of 14 RCTs comparing bisphosphonates treatment with a placebo treatment in patients with total knee arthroplasty (TKA) and THA, Lin et al. [
5] found that bisphosphonates reduced periprosthetic bone loss after TKA and THA. Although that finding was consistent with our research, that study was intended to investigate the efficacy and safety of bisphosphonates (alendronate, pamidronate, etidronate, zoledronate, risedronate, clodronate, and bisphosphonate) for patients with TKA and THA. Also, they only included one RCT that compared risedronate versus placebo for bone loss after THA and TKA. Thus, we could not conclude that risedronate had a significant influence on bone loss among patients with only THA. Zhao et al. [
1] conducted a similar meta-analysis about bisphosphonates for bone loss after THA; however, only one study comparing risedronate versus placebo was included in the meta-analysis. Therefore, large-scale trials are required to validate the effects of risedronate focus on patients with THA.
The duration of the follow-up in the included studies was ranged from 6 months to 4 years. Obviously, the relative short use of bisphosphonate will decrease the efficacy of anti-resorption. Eberhardt et al. [
19] reported that postoperative continuous and high-dose bisphosphonate treatment is potent in accelerating osseointegration of the prosthesis, which may prevent wear debris from migration by sealing the implant-bone interface. Friedl et al. [
20] however doubt that the long-term efficacy of bisphosphonate could reduce bone loss after THA. We also found that oral risedronate could increase the Harris hip scores compared with the control groups.
The limitations of our study include the following: (1) the BMD results from the meta-analysis of some ROI appeared heterogeneous, and sensitivity analysis and subgroup analyses failed to eliminate the heterogeneity; (2) the included studies did not have sufficient duration of risedronate treatment and follow-up and also lacked evaluating indexes like functional scores and the rate of revision, so we could not evaluate the efficacy of postoperative risedronate treatment comprehensively; and (3) the number and quality of the included RCTs were limited and thus future high-quality RCTs were still needed to identify the efficacy of risedronate for bone loss after THA.
Conclusions
In conclusion, oral risedronate could significantly reduce periprosthetic bone resorption around an uncemented femoral stem (Gruen zones 1, 2, 3, and 7) after THA. Due to the limited included studies and shortcoming of this meta-analysis, more high-quality RCTs are needed to identify the efficacy of risedronate for bone loss in THA.
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