Implant loosening is the most common indication for revision surgery after total hip arthroplasty (THA). Although bone resorption around the implants plays a pivotal role in the pathophysiology of loosening, it is unknown whether potent early inhibition of osteoclasts could mitigate this process and thus reduce the need for revision surgery. We performed a randomized, double-blind, placebo-controlled phase 2 trial in 64 patients aged 35 to 65 years with unilateral osteoarthritis of the hip. They underwent surgery with an uncemented THA and were randomized to either two subcutaneous doses of denosumab (n = 32) or placebo (n = 32) given 1 to 3 days and 6 months after surgery. Patients were followed for 24 months. Primary outcome was periprosthetic bone mineral density (BMD) of the hip at 12 months as measured by dual-energy X-ray absorptiometry (DXA). In addition, [ 18 F] sodium fluoride positron emission tomography/CT (F-PET) was performed in half of the patients for analysis of periprosthetic standardized uptake value (SUV). Analyses were made according to intention-to-treat principles. The trial was registered at ClinicalTrials.gov 2011-001481-18, NCT01630941. Denosumab potently inhibited early periprosthetic bone loss. After 12 months, BMD in the denosumab group was 32% (95% confidence interval [CI] 22-44) higher in Gruen zone 7 and 11% (95% CI 8-15) higher in zones 1 to 7. After 24 months, the difference in BMD between groups had decreased to 15% (95% CI 4-27) in zone 7 and 4% (95% CI 0-8) in zones 1 to 7. In both groups, SUV increased after surgery, but the increase was less pronounced in the denosumab group. Biochemical markers of bone metabolism decreased in the denosumab group in the first 12 months, but a rebound effect with marker concentrations above baseline was observed after 24 months. Denosumab potently prevents early periprosthetic bone loss after uncemented THA; however, the effect diminishes after discontinuation of treatment. Further research is needed to determine whether this bone loss will prove to be of clinical importance and, if so, whether the positive effect observed in this study could be preserved by either prolonged treatment with denosumab or additional antiresorptive treatment.

Background and purpose — We previously described a decrease in bone mineral density (BMD) in the calcar region 2 years after insertion of the collum femoris-preserving (CFP) stem, but the implants were stable. Now we have examined the long-term changes in periprosthetic BMD and stability of the CFP stem. Patients and methods — We conducted a minimum 8-year follow-up of 21 patients from our original investigation. We examined periprosthetic BMD by dual-energy X-ray absorptiometry (DEXA) and implant stability by radiostereometric analysis (RSA). Results — Between 2 and 8 years 1 stem was revised due to aseptic loosening. Between 2 and 8 years we found a 14% (95% confidence interval [CI] 9–19) reduction in BMD in Gruen zone 6 and 17% (CI 6–28) in Gruen zone 7. From baseline the reduction in BMD was 30% (CI 23–36) in Gruen zone 6, 39% (CI 31–47) in Gruen zone 7, and 19% (CI 14–23) in Gruen zone 2. Between 2 and 8 years, RSA (n = 17) showed a mean translation along the stem axis of 0.02mm (CI –0.02 to 0.06) and a mean rotation around the stem axis of 0.08° (CI –0.26 to 0.41). From baseline mean subsidence was 0.07 mm (CI –0.16 to 0.03) and mean rotation around the stem axis was 0.23° (CI –0.23 to 0.68) at 8 years. Interpretation — There was continuous loss of proximomedial BMD at 8 years while the CFP stem remained stable. Proximal periprosthetic bone loss cannot be prevented by this stem.

Background and purpose: Uncemented total hip arthroplasty (THA) is associated with periprosthetic bone loss. In a secondary outcome analysis from a randomized controlled trial, we studied whether denosumab can prevent loss of acetabular periprosthetic bone mineral density (pBMD) in patients who received a trabecular metal cup during uncemented THA.Patients and methods: 64 patients (aged 35–65 years) with unilateral osteoarthritis of the hip were randomized to 2 subcutaneous injections with denosumab or placebo, given 1–3 days post-surgery and 6 months post-surgery. Acetabular pBMD was measured in 5 regions of interest (ROIs) by dual-energy X-ray absorptiometry. Serum markers for bone metabolism were analyzed. Periprosthetic osteoblastic activity, measured as standardized uptake values (SUVs) by [18F] positron emission tomography/computed tomography, was evaluated in 32 of the 64 study patients.Results: After 12 months, patients treated with denosumab had higher pBMD compared with the placebo-treated patients in 4 of 5 ROIs and in sum of ROIs 1–5. After 24 months, the effect on pBMD for patients treated with denosumab declined. Serum markers declined pronouncedly up to 12 months in patients treated with denosumab, but rebounded above baseline levels after 24 months. Patients treated with denosumab had statistically significantly lower SUVs in all ROIs, except ROI 5, after 6 months.Interpretation: Based on this exploratory analysis of secondary endpoints the application of denosumab seems associated with preserved acetabular pBMD, reduced bone metabolism and attenuated periprosthetic osteoblastic activity. However, given the known rebound affects after discontinuation of denosumab treatment, these effects cannot be expected to persist. If prolonged treatment or shift to other regimes would be beneficial to reduce the risk of cup loosening is yet to be investigated.