Bone mechanics bone strength and beyond

Transcription

1 Bone mechanics bone strength and beyond Tim Arnett Bone Curriculum Symposium 2018 Department of Cell & Developmental Biology University College London

2 Factors affecting bone strength Mass Architectural quality - shape, trabecular connectedness and orientation Lamellar vs. woven bone Microcracks Collagen quality: X-links and AGEs? Degree / heterogeneity of mineralisation; crystal size? Toughness

3 Trabecular bone turnover in osteoporosis enhanced resorption

4 Low-power scanning electron microscope image of normal bone architecture in the 3rd lumbar vertebra of a 30 year old womanerconnected plates of bone

5 Low-power scanning electron microscope image of osteoporotic bone architecture in the 3rd lumbar vertebra of a 71 year old womanerconnected plates of bone

6 Trabcular bone element eroded by osteoclasts micro fracture

7 Trabcular bone element perforated by osteoclast action

8 Normal bone architecture in 3rd lumbar vertebra of 30 year old woman (GIF) marrow and other cells removed Prof Alan Boyde QMUL Alan Boyde, QMUL

9 Osteoporotic bone architecture in 3rd lumbar vertebra of 89 year old woman (GIF) Prof Alan Boyde QMUL

10 Osteoporotic bone architecture in 3rd lumbar vertebra of 89 year old woman (GIF) Prof Alan Boyde QMUL

11 Loading, stress & strain Strain is the response of a system to an applied stress. When a material is loaded with a force, it produces a stress, which then causes the material to deform. Stress modes: compressive, tensile, shear / bending Strain ( ) is defined by engineers as the amount of deformation in the direction of the applied force divided by the initial length of the material.

12 Resistance to bending AGEING endosteal bone resorption periosteal bone formation cortex area = 100% cortex area = 88% Stiffness = 100% Stiffness = 117% Adapted from Turner CH (2006) Ann NY Acad Sci 1068:

13 Stress Toughness of bone Toughness is the ability of a material to absorb energy and deform plastically without fracturing. May be defined as the amount of energy per unit volume that a material can absorb before rupturing. In bone, toughness is related to - collagen orientation (lamellar is best) - microcracks - collagen quality - degree and heterogeneity of mineralisation Toughness = area under curve Strain

14 Micro-cracks Meier (2008) J Biomech Thought to have a critical effect on overall toughness (resistance to fracture) of bones. Cortical bone fractures may begin as a microcrack that enlarges explosively under mechanical load - eg, a fall. Burr DB (2011) J Musculoskelet Neuronal Interact 11: Reeve J (2017) BoneKEy Reports 6, Article #867

15 Secondary mineralisation Backscattered electron SEM imaging - old bone more highly mineralised - reflects electrons (appears white) NB artifactual cracks! Bone & Joint Research Lab University of Utah Excessive mineralisation can affect material properties of bone, making it more brittle Excessive mineral homogeneity may aid crack propagation

16 Wolff s law Orthopaedic surgeon at Charité, Berlin. Postulated (1892) that bone grows and remodels in response to the forces that are placed upon it. Julius Wolff ( ) Bone is deposited at sites where it is required and resorbed where it is not.

17 Trabecular architecture in human femur Alignment of trabeculae along lines of loading stress in femoral neck & trochanter (Wolff s Law)

18 Mechanical loading and osteogenesis Mechanical loading is the main physiological factor regulating bone homeostasis Frost - bone mechanostat hypothesis bone remodels to achieve target strain levels Lanyon - implanted strain gauges in bone and showed that maximum physiological deformation under load is ~3000 -strain (ie, 0.3%) Lanyon - showed that dynamic, cyclical loads strain are powerfully osteogenic; suggested that osteocyte network functions as mechanosensor Osteogenic response strongest to higher strain rates and loads at upper end of normal range impact loading Bones of professional tennis players heavier and stronger in the playing arm Frost HM (1987) Bone mass and the mechanostat. Anat Rec 219: 1-9 Ehrlich PJ, Lanyon LE (2002) Mechanical strain and bone cell function. Osteoporos Int 13:

19 Experimental demonstration of osteogenic effect of mechanical loading of bones Strain gauges Invasive loading isolated turkey ulna 36 loading cycles / day at 0.5 Hz sufficient to prevent disuse bone loss and promote significant osteogenesis Non-invasive loading mouse tibia Rubin CT, Lanyon LE (1984) J Bone Joint Surg Am 66: Meakin LB et al (2014) Frontiers in Endocrinology / Bone Research 5: article 154

20 Osteocytes - cells resident in bone Communicate with each other and with osteoblasts via fine canaliculi Are thought to detect strain in bone (ie, deformation) resulting from loading and co-ordinate adaptive remodelling... but still no formal proof of this hypothesis! Reduced loading may lead to osteocyte cell death DIPHTHERIA TOXIN & OSTEOCYTES Al-Jazzar A et al (2017) Int J Mol Sci Tatsumi S et al (2007) Cell Metab Asada N et al (2013) Cell Stem Cell Sato M et al (2013) Cell Metab

21 Age-related changes to material properties of bone Accumulation of old, more highly mineralised bone in low turnover situations Decreased collagen content Changes to collagen chemistry increased enzymatic (pyridinium) and non-enzymatic (*AGEs) X-links Do these changes make bone more prone to fracture? * Advanced Glycation Endproducts are protein glycosylations eg, pentosidine (derived from ribose), which forms fluorescent cross-links between arginine and lysine residues in collagen

22 Effect of age on collagen and cross-links from human bone Normal cortical bone from 40 normal male cadavers - Nyman et al (2006) Bone 39:

23 Reduced bone quality & stiffness in osteogenesis imperfecta (oim) mice Mice bear mutation in gene encoding α-2 chain of type I procollagen mild OI Tibial growth plate 8 weeks Ranzoni et al (2016) Scientific Reports

24 Beyond

25 Thank you!