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Uniaxial and Multiaxial Fatigue Life Prediction of the Trabecular Bone Based on Physiological Loading: A Comparative Study

Fatihhi SJ, Harun MN, Abdul Kadir MR, Abdullah J, Kamarul T, Öchsner A, et al.

Ann Biomed Eng, 2015 Oct;43(10):2487-502.
PMID: 25828397 DOI: 10.1007/s10439-015-1305-8

Fatigue assessment of the trabecular bone has been developed to give a better understanding of bone properties. While most fatigue studies are relying on uniaxial compressive load as the method of assessment, in various cases details are missing, or the uniaxial results are not very realistic. In this paper, the effect of three different load histories from physiological loading applied on the trabecular bone were studied in order to predict the first failure surface and the fatigue lifetime. The fatigue behaviour of the trabecular bone under uniaxial load was compared to that of multiaxial load using a finite element simulation. The plastic strain was found localized at the trabecular structure under multiaxial load. On average, applying multiaxial loads reduced more than five times the fatigue life of the trabecular bone. The results provide evidence that multiaxial loading is dominated in the low cycle fatigue in contrast to the uniaxial one. Both bone volume fraction and structural model index were best predictors of failure (p

Matched MeSH terms: Bone and Bones/physiopathology*
Mechanical and microarchitectural analyses of cancellous bone through experiment and computer simulation

Syahrom A, Abdul Kadir MR, Abdullah J, Öchsner A

Med Biol Eng Comput, 2011 Dec;49(12):1393-403.
PMID: 21947767 DOI: 10.1007/s11517-011-0833-0

The relationship between microarchitecture to the failure mechanism and mechanical properties can be assessed through experimental and computational methods. In this study, both methods were utilised using bovine cadavers. Twenty four samples of cancellous bone were extracted from fresh bovine and the samples were cleaned from excessive marrow. Uniaxial compression testing was performed with displacement control. After mechanical testing, each specimen was ashed in a furnace. Four of the samples were exemplarily scanned using micro-computed tomography (μCT) and three dimensional models of the cancellous bones were reconstructed for finite element simulation. The mechanical properties and the failure modes obtained from numerical simulations were then compared to the experiments. Correlations between microarchitectural parameters to the mechanical properties and failure modes were then made. The Young's modulus correlates well with the bone volume fraction with R² = 0.615 and P value 0.013. Three different types of failure modes of cancellous bone were observed: oblique fracture (21.7%), perpendicular global fracture (47.8%), and scattered localised fracture (30.4%). However, no correlations were found between the failure modes to the morphological parameters. The percentage of error between computer predictions and the actual experimental test was from 6 to 12%. These mechanical properties and information on failure modes can be used for the development of synthetic cancellous bone.

Matched MeSH terms: Bone and Bones/physiopathology*
Mechanical and functional assessment of the wrist affected by rheumatoid arthritis: A finite element analysis

Bajuri MN, Kadir MR, Raman MM, Kamarul T

Med Eng Phys, 2012 Nov;34(9):1294-302.
PMID: 22277308 DOI: 10.1016/j.medengphy.2011.12.020

Understanding the pathomechanics involved in rheumatoid arthritis (RA) of the wrist provides valuable information, which will invariably allow various therapeutic possibilities to be explored. The computational modelling of this disease permits the appropriate simulation to be conducted seamlessly. A study that underpins the fundamental concept that produces the biomechanical changes in a rheumatoid wrist was thus conducted through the use of finite element method. The RA model was constructed from computed tomography datasets, taking into account three major characteristics: synovial proliferation, cartilage destruction and ligamentous laxity. As control, a healthy wrist joint model was developed in parallel and compared. Cartilage was modelled based on the shape of the articulation while the ligaments were modelled with linear spring elements. A load-controlled analysis was performed simulating physiological hand grip loading conditions. The results demonstrated that the diseased model produced abnormal wrist extension and stress distribution as compared to the healthy wrist model. Due to the weakening of the ligaments, destruction of the cartilage and lower bone density, the altered biomechanical stresses were particularly evident at the radioscaphoid and capitolunate articulations which correlate to clinical findings. These results demonstrate the robust finding of the developed RA wrist model, which accurately predicted the pathological process.

Matched MeSH terms: Bone and Bones/physiopathology
Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism

Hasan WNW, Chin KY, Jolly JJ, Ghafar NA, Soelaiman IN

Endocr Metab Immune Disord Drug Targets, 2018;18(5):450-457.
PMID: 29683099 DOI: 10.2174/1871530318666180423122409

BACKGROUND: Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling.
OBJECTIVE: This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.
DISCUSSION: Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.
CONCLUSION: Mevalonate pathway can be exploited to develop effective antiosteoporosis agents.

Matched MeSH terms: Bone and Bones/physiopathology
Effects of pharmaceutical care on adherence and persistence to bisphosphonates in postmenopausal osteoporotic women

Lai PS, Chua SS, Chew YY, Chan SP

J Clin Pharm Ther, 2011 Oct;36(5):557-67.
PMID: 21916908 DOI: 10.1111/j.1365-2710.2010.01210.x

Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy, but the association between adherence and bone turnover markers (BTMs) has never been studied. Therefore, the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence (and its effects on BTMs), as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates.

Matched MeSH terms: Bone and Bones/physiopathology
A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus

Mansur SA, Mieczkowska A, Flatt PR, Bouvard B, Chappard D, Irwin N, et al.

Bone, 2016 06;87:102-13.
PMID: 27062994 DOI: 10.1016/j.bone.2016.04.001

Obesity and type 2 diabetes mellitus (T2DM) progress worldwide with detrimental effects on several physiological systems including bone tissue mainly by affecting bone quality. Several gut hormones analogues have been proven potent in ameliorating bone quality. In the present study, we used the leptin receptor-deficient db/db mice as a model of obesity and severe T2DM to assess the extent of bone quality alterations at the organ and tissue levels. We also examined the beneficial effects of gut hormone therapy in this model by using a new triple agonist ([d-Ala(2)]GIP-Oxm) active at the GIP, GLP-1 and glucagon receptors. As expected, db/db mice presented with dramatic alterations of bone strength at the organ level associated with deterioration of trabecular and cortical microarchitectures and an augmentation in osteoclast numbers. At the tissue level, these animals presented also with alterations of bone strength (reduced hardness, indentation modulus and dissipated energy) with modifications of tissue mineral distribution, collagen glycation and collagen maturity. The use of [d-Ala(2)]GIP-Oxm considerably improved bone strength at the organ level with modest effects on trabecular microarchitecture. At the tissue level, [d-Ala(2)]GIP-Oxm ameliorated bone strength reductions with positive effects on collagen glycation and collagen maturity. This study provides support for including gut hormone analogues as possible new therapeutic strategies for improving bone quality in bone complications associated to T2DM.

Matched MeSH terms: Bone and Bones/physiopathology*
Orthosiphon stamineus (Misai Kucing) ameliorated postmenopausal osteoporosis in rat model

Bokhari RA, Lau SF, Mohamed S

Menopause, 2018 02;25(2):202-210.
PMID: 28926512 DOI: 10.1097/GME.0000000000000980

OBJECTIVE: Orthosiphon stamineus (OS) or Misai Kucing (Java tea) is a popular herbal supplement from Southeast Asia for various metabolic, age-related diseases. This study investigated the potential use of OS leaf extracts to ameliorate osteoporosis in ovariectomized rats.
METHODS: Fifty-six female Sprague-Dawley rats were randomly allocated into eight groups (n = 7): SHAM (healthy sham control); OVX (ovarietomized) nontreated rats (negative control); OVX + Remifemin (100 mg/kg body weight), and 2% green tea extract (positive controls); OVX + OS 50% ethanolic and aqueous extracts, both at either 150 or 300 mg/kg. After 16 weeks, the rats' bones and blood were evaluated for osteoporosis indicators (protein and mRNA expressions), micro-computed tomography for bone histomorphometry, and three-point bending test for tibia mechanical strength.
RESULTS: The extracts dose-dependently and significantly (P bone strength and flexibility, bone mineral density, bone formation protein markers (P1NP), and bone histomorphometry. All extracts reduced the inflammation biomarker (interleukin-6). The extracts up-regulated osteoblastogenesis (bone morphogenetic protein-2) and collagen-1 synthesis (collagen type 1 alpha-1) mRNA expressions, and down-regulated bone resorption (TNFSF11 and nuclear factor-kappa B) mRNA expressions. Both the water and 50% ethanolic extract were effective. The effective dose is equivalent to 25 to 50 mg/kg extract for humans.
CONCLUSIONS: The extract showed bone-protective and antiosteoporotic effects (improving bone strength, flexibility, bone density, and bone morphometry) by reducing inflammation and the bone resorption biomarkers, while enhancing bone formation biomarkers and collagen synthesis.

Matched MeSH terms: Bone and Bones/physiopathology