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Bone & Joint Research
Vol. 12, Issue 9 | Pages 536 - 545
8 Sep 2023
Luo P Yuan Q Yang M Wan X Xu P

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 826 - 834
17 Nov 2022
Kawai T Nishitani K Okuzu Y Goto K Kuroda Y Kuriyama S Nakamura S Matsuda S

Aims

The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip.

Methods

We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model.


The Bone & Joint Journal
Vol. 104-B, Issue 11 | Pages 1225 - 1233
1 Nov 2022
Png ME Petrou S Achten J Ooms A Lamb SE Hedley H Dias J Costa ML

Aims

The aim of this study was to compare the cost-effectiveness of surgical fixation with Kirschner (K-)wire ersus moulded casting after manipulation of a fracture of the distal radius in an operating theatre setting.

Methods

An economic evaluation was conducted based on data collected from the Distal Radius Acute Fracture Fixation Trial 2 (DRAFFT2) multicentre randomized controlled trial in the UK. Resource use was collected at three, six, and 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from an NHS and personal social services perspective. Sensitivity analyses were conducted to examine the robustness of cost-effectiveness estimates, and decision uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves.


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1648 - 1655
1 Nov 2021
Jeong S Hwang K Oh C Kim J Sohn OJ Kim JW Cho Y Park KC

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.


Bone & Joint Open
Vol. 1, Issue 9 | Pages 512 - 519
1 Sep 2020
Monzem S Ballester RY Javaheri B Poulet B Sônego DA Pitsillides AA Souza RL

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Methods

Three groups (seven per group) of 12-week-old mice were: 1) ovariectomized and 20 weeks thereafter treated weekly for 24 weeks with 100 μm/kg subcutaneous ibandronate (OVX+IBN); 2) ovariectomized (OVX); or 3) sham-operated (SHAM). Quantitative fracture analysis generated biomechanical properties for the femoral neck. Tibiae were microCT scanned and trabecular (proximal metaphysis) and cortical parameters along almost its whole length measured.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1285 - 1291
1 Oct 2019
MacKenzie SA Ng RT Snowden G Powell-Bowns MFR Duckworth AD Scott CEH

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.


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 147 - 153
1 Feb 2019
Mai DH Oh C Doany ME Rokito AS Kwon YW Zuckerman JD Virk MS

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).


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.


Bone & Joint Research
Vol. 7, Issue 10 | Pages 548 - 560
1 Oct 2018
Qayoom I Raina DB Širka A Tarasevičius Š Tägil M Kumar A Lidgren L

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 406 - 413
1 Jun 2018
Shabestari M Kise NJ Landin MA Sesseng S Hellund JC Reseland JE Eriksen EF Haugen IK

Objectives

Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA.

Methods

Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 452 - 463
1 Jul 2017
Wang G Sui L Gai P Li G Qi X Jiang X

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Methods

We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.


The Bone & Joint Journal
Vol. 99-B, Issue 3 | Pages 295 - 302
1 Mar 2017
Koh A Guerado E Giannoudis PV

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.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 144 - 153
1 Mar 2017
Kharwadkar N Mayne B Lawrence JE Khanduja V

Objectives

Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.

Methods

We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 160 - 165
1 Feb 2016
Farrier AJ C. Sanchez Franco L Shoaib A Gulati V Johnson N Uzoigwe CE Choudhury MZ

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.


Bone & Joint 360
Vol. 4, Issue 2 | Pages 17 - 20
1 Apr 2015

The April 2015 Wrist & Hand Roundup360 looks at: Non-operative hand fracture management; From the sublime to the ridiculous?; A novel approach to carpal tunnel decompression; Osteoporosis and functional scores in the distal radius; Ulnar variance and force distribution; Tourniquets in carpal tunnel under the spotlight; Scaphoid fractures reclassified; Osteoporosis and distal radial fracture fixation; PROMISing results in the upper limb


Bone & Joint 360
Vol. 4, Issue 2 | Pages 32 - 34
1 Apr 2015

The April 2015 Research Roundup360 looks at: MCID in grip strength and distal radial fracture; Experiencing rehab in a trial setting; Electrical stimulation and nerve recovery; Molecular diagnosis of TB?; Acetabular orientation: component and arthritis; Analgesia after knee arthroplasty; Bisphosphonate-associated femoral fractures


The Bone & Joint Journal
Vol. 96-B, Issue 8 | Pages 1035 - 1040
1 Aug 2014
Meling T Nawab A Harboe K Fosse L

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.


Bone & Joint 360
Vol. 3, Issue 1 | Pages 14 - 17
1 Feb 2014

The February 2014 Hip & Pelvis Roundup360 looks at: length of stay; cementless metaphyseal fixation; mortality trends in over 400,000 total hip replacements; antibiotics in hip fracture surgery; blood supply to the femoral head after dislocation; resurfacing and THR in metal-on-metal replacement; diabetes and hip replacement; bone remodelling over two decades following hip replacement; and whether bisphosphonates affect acetabular fixation.


Bone & Joint 360
Vol. 2, Issue 5 | Pages 37 - 39
1 Oct 2013

The October 2013 Children’s orthopaedics Roundup360 looks at: Half a century of Pavlik treatment; Step away from the child!: trends in fracture management; Posterolateral rotatory elbow instability in children; Osteochondral lesions undiagnosed in patellar dislocations; Oral bisphosphonates in osteogenesis imperfecta; Crossed or parallel pins in supracondylar fractures?; Not too late nor too early: getting epiphysiodesis right; Fixation of supramalleolar osteotomies.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 75 - 75
1 Sep 2012
Delisle J Fernandes JC Troyanov Y Perreault S
Full Access

Purpose. In 2010, the new clinical guideline of Osteoporosis Canada for the diagnosis of osteoporosis, clearly indicates that patients with high-risk of fracture are those that have already sustained a fracture (osteoporotic fracture). Until now, only 12% of the 3,400 fractures that we treat each year receive a treatment for osteoporosis. We are validating an evaluation protocol and a multidisciplinary systematic follow-up approach for osteoporosis. Patients are managed by a clinical nurse specialist. We are recruiting 543 patients with an osteoporotic fracture at Hal du Sacré-Coeur de Montréal. We aim to evaluate: 1) the incidence of a second osteoporotic fracture, 2) the initiation of a treatment and determine the compliance and adherence to treatment and 3) the evaluation of CTX-1 and Osteocalcin at Baseline, 6, 12,18 et 24 months (treatment efficacy) and 4) the functional outcome and quality of life post-fracture. Method. We've enrolled 153 subjects (men and women) over 40 years of age who were treated for an osteoporotic fracture at the orthopaedic clinic of Hal du Sacré-Coeur de Montréal. After starting a treatment protocol for osteoporosis, the subjects will be followed for a 24 months period at different time intervals. During these visits, they fill up functional outcome questionnaires, undergo physical exam, blood test, x rays and their compliance to treatment is evaluated. Results. Mean patients age was 65 y.o (+ 13). Two hundred seventeen patients were approached and 153 patients were enrolled (23 men and 130 women). Eleven patients refused to be part of the systematic follow up because they were satisfied with their family doctors osteoporosis management. Fifty-three were explained treatment and follow up and refused to participate. Thirteen patients (9%) dropped out after six months. One patient died. Twenty-one patients (13.7%) were already on bisphosphonates and 53 pts (34.6 %) had already sustained a fragility fracture. All patients were prescribed risedronate except three that were prescribed zoledronic acid or pamidronate for intolerance or contraindication to oral bisphosphonates. Up to now, we obtained 71% adherence and 91% persistence. After validation, 10% of the patients needed to be referred to a rheumatologist and 90% of the patients were managed by the clinical nurse specialist. Conclusion. Our multidisciplinary systematic follow up of osteoporotic fracture improved the osteoporosis treatment rate from 12 to 71 % in our orthopaedic surgery department. Clinical Nurse Specialists could represent the best approach to manage the underlying osteoporosis that leads to fragility fractures