Normal Bone Physiology and Anatomy Normal Bone • Dynamic: constant resorption, renewal and remodelling • Inner architecture o Periosteum: fibrous cover o Cortex: thick outer layer of compact bone o Medulla: inner cavity, cancellous (spongey) bone: trabeculae separated by marrow • Composition o Matrix: osteoid, mineral o Cells: osteoblasts, osteocytes, osteoclasts • Osteoid o Type 1 collagen o Osteocalcin (mineralisation, osteoblastic activity) o Cytokines and GFs: transfer mechanical and metabolic signals into bone cell activity (mechanotransduction) o Mineralises to calcium hydroxyapatite (Ca under regulation by PTH, vitD, calcitriol) • Osteoblasts o Cover surface of bone o Most common/predominant cell o Produce collagen and other elements in matrix o Involved in mineralised o Receptors for PTH, vitD, cytokines, GFs o Regulate osteoclast activity • Osteocytes o Derived from osteoblasts o Entrapped within newly formed bone matrix o Communicate via cell cytoplasmic processes o Local Ca and PO43 control o Mechanotransduction • Osteoclasts o Multinucleated giant cells o Bone marrow derived: monocyte/macrophage lineage o 2 week lifespan o Reabsorbs bone in depressions on bone surface called Howship lacunae which are highly acidic RANK and OPG • Bone resorption/formation is the balance between RANK and OPG activity • RANKL & M-CSF favour osteoclast differentiation and bone resorption • OPG blocks RANKL-RANK interaction • OPG production is under WNT/β-catenin control • OPG and RANKL influenced by: hormones, vitD, cytokines, GFs • Local control: bone matrix degradation by osteoclasts releases cytokines and GFs which activate osteoblasts Two Macroscopic Bone Types • Lamellar o Forms mature skeleton (compact and cancellous) o Collagen fibres laid down in ordered parallel sheets (lamellae) o Direction of fibres differ in sheets o Moderately cellular • Woven o Immature: developing skeleton, initial fracture union, pathological rapid bone formation o Fibres randomly oriented, resists force equally in all directions o Highly cellular o Gradually replaced by lamellar bone during growth o Weaker than lamellar bone Fives Zones of Endochondral Ossification 1. Zone of reserve cartilage 2. Zone of proliferation 3. Zone of hypertrophy and maturation 4. Zone of calcification and degradation of cartilage 5. Zone of ossification Calcitonin • Hormone from thyroid parafollicular C cells • ↑Ca absorption into bone • ↓Osteoclast activity Vitamin D • Fat soluble • Maintain plasma Ca and PO43- o ↑Ca and PO43- absorption in GIT o ↑Ca renal absorption o ↑Osteoblast RANKL expression o ↑Osteoblast osteocalcin expression  mineralisation • Neural excitation and muscle relaxation • UVB skin exposure is main source • Conversion to active form influence by: o PTH o ↓Phosphorus PTH • Chief cells from parathyroid gland • Negative feedback loop with ionised blood Ca • Maintain plasma Ca levels o ↑Intestinal Ca absorption o ↑Renal Ca reabsorption o ↑Renal phosphorus excretion o ↑RANKL osteoblast expression o ↓Osteoblast OPG expression