Dataset Information

Denosumab prevents acetabular bone loss around an uncemented cup: analysis of secondary outcomes in a randomized controlled trial.

ABSTRACT:

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.

SUBMITTER: Kiritopoulos D

PROVIDER: S-EPMC9450252 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Denosumab prevents acetabular bone loss around an uncemented cup: analysis of secondary outcomes in a randomized controlled trial.

Kiritopoulos Demostenis D Nyström Andreas A Ullmark Gösta G Sörensen Jens J Petrén-Mallmin Marianne M Milbrink Jan J Hailer Nils P NP Mallmin Hans H

Acta orthopaedica 20220907

<h4>Background and purpose</h4>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.<h4>Patients and methods</h4>64 patients (aged 35-65 years) with unilateral osteoarthritis of the hip were randomized to 2 subcutaneous injecti ...[more]

PMID: 36069479

Similar Datasets

Project description:Background: Acetabular cage reconstruction with bone allografts is among the successful strategies to deal with massive acetabular bone loss. However, the nonbiological fixation nature of cages can compromise long-term success. Tantalum trabecular metal acetabular cups (TM cups) have been used in acetabular revision surgery because of their increased initial stability and good bone ingrowth features. This study was performed to determine whether the bone stock of the acetabulum is enough to support a hemispheric TM cup after failed cage reconstruction with bone allografts. Methods: We retrospectively reviewed patients who received acetabular revision surgery with TM cups after failed cage reconstruction with bone allografts from 2006 to 2017. There were 12 patients (5 males and 7 females) included in this study, with a mean age of 61.5 years (38 to 81) at the time of re-revision surgery. The mean follow-up after re-revision surgery was 8.6 years (2.6 to 13.3). The endpoint was defined as the aseptic loosening of the TM cup and reoperation for any causes. The change in bone stock of the acetabulum between index revision and re-revision was assessed according to the Gross classification for acetabular bone loss. Results: One patient died after eight years of follow-up of a cause not related to hip surgery. Two patients received two-stage revision arthroplasty due to PJI after 3.2 and 9.4 years of follow-up, respectively. The bone stock of the acetabulum was significantly improved between index revision and re-revision surgery (p < 0.0001). The Kaplan-Meier survivorship was 100% with aseptic loosening as the endpoint and 90% and 75% at five- and ten-year follow-up, respectively, with reoperation for any reason as the endpoint. Even cage reconstruction with bone allografts will fail eventually, and the bone stock of the acetabulum will improve after union and incorporation between host bone and allografts. The restored bone stocks will facilitate further revision surgery with hemispheric TM cups. The biological fixation between host bone and tantalum trabecular metal can provide longstanding stability of the TM cup. Conclusions: The results of our study offer a viable option for patients with failed cage reconstruction with bone allografts.

Project description:Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033. Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life. Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Project description:Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness. The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection. The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose. D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.

Dataset Information

Denosumab prevents acetabular bone loss around an uncemented cup: analysis of secondary outcomes in a randomized controlled trial.

Background and purpose

Patients and methods

Results

Interpretation

Publications

Denosumab prevents acetabular bone loss around an uncemented cup: analysis of secondary outcomes in a randomized controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets