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Bone & Joint Research
Vol. 6, Issue 10 | Pages 602 - 609
1 Oct 2017
Jin A Cobb J Hansen U Bhattacharya R Reinhard C Vo N Atwood R Li J Karunaratne A Wiles C Abel R

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 6, Issue 9 | Pages 542 - 549
1 Sep 2017
Arnold M Zhao S Ma S Giuliani F Hansen U Cobb JP Abel RL Boughton O

Objectives

Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness.

Methods

A systematic review of all English language articles using a keyword search was undertaken using Medline, Embase, PubMed, Scopus and Cochrane databases. Studies that only used nanoindentation, cancellous bone or animal tissue were excluded.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 6 - 11
1 Jan 2018
Wong RMY Choy MHV Li MCM Leung K K-H. Chow S Cheung W Cheng JCY

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Materials and Methods

A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted.


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.


Bone & Joint Research
Vol. 6, Issue 6 | Pages 366 - 375
1 Jun 2017
Neves N Linhares D Costa G Ribeiro CC Barbosa MA

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Methods

A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 14 - 21
1 Jan 2017
Osagie-Clouard L Sanghani A Coathup M Briggs T Bostrom M Blunn G

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.

Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 57 - 65
1 Jan 2017
Gumucio JP Flood MD Bedi A Kramer HF Russell AJ Mendias CL

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Methods

Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 538 - 543
1 Nov 2016
Weeks BK Hirsch R Nogueira RC Beck BR

Objectives

The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity.

Methods

A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings.


Bone & Joint Research
Vol. 1, Issue 2 | Pages 13 - 19
1 Feb 2012
Smith MD Baldassarri S Anez-Bustillos L Tseng A Entezari V Zurakowski D Snyder BD Nazarian A

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

Methods

A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity.