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      No effect of risedronate on femoral periprosthetic bone loss following total hip arthroplasty : A 4-year follow-up of 61 patients in a double-blind, randomized placebo-controlled trial

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          Abstract

          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.

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          Most cited references21

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          Fracture risk remains reduced one year after discontinuation of risedronate.

          One year after discontinuation of three year's treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients. Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers--bone mineral density (BMD) and bone turnover markers (BTM)--and fracture risk after discontinuation of treatment with risedronate. Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later. In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p < or = 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]). Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.
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            Continuous bone loss around a tapered uncemented femoral stem: a long-term evaluation with DEXA.

            Periprosthetic bone loss is a well-documented phenomenon after uncemented total hip arthroplasty (THA); however, little is known about how bone mineral density (BMD) changes after 2 years. 14 patients with hip arthrosis (group A) were operated with a proximally porous- and hydroxyapatite-coated stem and followed for 10 years with DEXA, radiographs and Harris hip score (HHS). Another group of 14 patients (group B) was evaluated at 6 and 14 years using the same prosthesis and protocol. No stem was revised and all stems were well-Fixed. At final follow-up, HHS was 97 points in group A after 10 years and 94 points in group B after 14 years. Bone mineral changes in group A were greatest in Gruen zones 1 and 7, where the losses were 31% and 26%, respectively, after 2 years on the operated side. The decrease in BMD continued after 2 years and in Gruen zone 7 it was faster than the rate of bone loss on the control side. In group B, the annual change in BMD on the operated side was not significantly different from the bone loss in group A. Up to 14 years after implantation of a tapered uncemented stem, the BMD in the calcar region continues to decrease faster than would be expected from normal ageing.
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              Atypical fractures as a potential complication of long-term bisphosphonate therapy.

              The development of bisphosphonate therapy represented an important advance in the treatment of low bone mass and osteoporosis, conditions that affect more than half of individuals older than 50 years. Currently available bisphosphonates have been shown to reduce spine, nonspine, and hip fractures in individuals at increased risk of fracture. Case reports and limited clinical series over the past 5 years have raised concern that prolonged bisphosphonate therapy may suppress bone remodeling to the extent that normal bone repair is impaired, resulting in increased fracture risk. Fractures potentially resulting from suppressed bone turnover have been described as "atypical," affecting sites such as the subtrochanteric femur that are infrequently affected by osteoporotic fractures. A prodrome of thigh pain, lack of trauma prior to the fracture, and specific radiological characteristics have also been reported. Data are limited on the prevalence of, risk factors for, and treatment of this potential problem. Current strategies include fracture risk assessment, targeting bisphosphonate therapy appropriately to individuals at increased risk of fracture, considering a 12-month interruption in therapy after 5 years in patients who are clinically stable, and considering teriparatide treatment in individuals who experience an atypical fracture while receiving bisphosphonate therapy.
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                Author and article information

                Journal
                Acta Orthop
                Acta Orthop
                ORT
                Acta Orthopaedica
                Informa Healthcare
                1745-3674
                1745-3682
                October 2015
                04 September 2015
                : 86
                : 5
                : 569-574
                Affiliations
                Division of Orthopedics , Department of Clinical Sciences, Danderyd Hospital and the Karolinska Institute, Stockholm, Sweden
                Author notes
                Article
                ORT_A_1041846_O
                10.3109/17453674.2015.1041846
                4564779
                25885280
                b168e898-e065-4b70-b8a2-3035fa138b5c
                Copyright: © Nordic Orthopaedic Federation

                This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.

                History
                : 16 September 2014
                : 14 March 2015
                Categories
                Hip

                Orthopedics
                Orthopedics

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