see also:

• calcium
• orthopaedics in the ED
• osteoporosis

• special form of connective tissue made of collagenous matrix impregnated with mineral salts, esp. calcium phosphates;
• mainly hydroxyapatite Ca^10-x (H₂0)^2x (PO₄)⁶ (OH)² ⇒ 20 x 3-7 nm crystals;
• trabecular bone (25%) bone is lost from most readily;
• compact bone (75%) denser, less active metabolically;
• nutrients provided via Haversian canal which are blood vessels surrounded by concentric layers of collagen forming osteons or Haversian systems;

• Arise from mesenchymal osteoprogenitor stem cells and form bone by secreting collagen, forming a matrix around themselves which then calcifies, and then they are called osteocytes;
• Have processes that are sent along canaliculi, and ramify throughout bone, connect to other processes via tight junctions;
• Hox genes play a major role in determining when and how much these stem cells divide and form osteoblasts
  • it seems the stem cells in the periosteum (PSPCs) rather than those in the marrow are most important in fracture repair
  • PSPCs exist as a mixed stem cell population that includes those with the most stemness, naive periosteal stem cells (PSCs), alongside more mature periosteal progenitor 1 and 2 (PP1 and PP2) cells
  • Hoxa10 expression is most abundant in PSCs and was significantly reduced as cells progressed along the lineage hierarchy to PP1 and PP2
  • Hox protein deficiency leads to an increase in the stem cells' propensity to differentiate into mature bone cell types and reduced ability to repair fractures
  • increasing Hoxa10 expression in tibia stem and progenitor cells, reprogrammed them into a more stem cell-like state, a needed step if they are to become new bone-making cells as part of healing and in aging mice caused a 33% restoration of fracture repair capacity ¹⁾

• Multinuclear cells that erode & resorb previously formed bone and derived from monocytes;

• Throughout life, bone is constantly being resorbed and new bone formed;
• Bone calcium turnover is 100% /yr infants; and 18%/yr adults;
• Renewal rates: compact bone 4%/yr; trabecular bone 29%/yr;
• Remodeling partly related to stresses and strains, & regulated by:
  • hormones:
    • parathyroid hormone (PTH) ⇒ mobilisation Ca & P from bone;
    • growth hormone ⇒ incr.prolif. cartilage in epiph.plate'
    • calcitonin ⇒ inhibits bone resorption;
    • 1,25 dihydroxycholecalciferol ⇒ incr. osteoblast factors
      • ⇒ mobilisation calcium & phosphate from bone;
  • local growth factors (? paracrine fashion):
    • fibroblast growth factors (FGF);
    • transforming growth factors (TGF);
    • insulin-like growth factors (IGF) ⇒ incr. collagen;
    • beta2-microglobulin (beta2m);
    • platelet derived growth factor (PDGF);
    • interleukin-1B (IL-1B) ⇒ activates osteoclasts;
    • gamma interferon (IFN-gamma);
    • prostaglandins?
    • osteoprotegerin (OPG) (aka osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B) )
      • a secreted glycoprotein in the tumor necrosis factor receptor superfamily which operates as a soluble decoy receptor
      • regulates bone metabolism by suppressing the formation and activation of osteoclasts
      • beyond its roles in bone physiology, OPG is expressed in vascular smooth muscle cells (VSMCs), endothelial cells, and cardiomyocytes
      • granulocytes secrete interleukin-17 (IL-17), which enhances the recruitment of immune cells and the synthesis of OPG in vascular and immunological tissues. IL-17 does not establish a closed loop but instead activates the production of pro-inflammatory mediators, including OPG, by endothelial cells (ECs), macrophages, and granulocytes.
      • OPG levels might potentially serve as a biomarker of vascular stress and remodeling rather than a pathogenic cause
      • elevated OPG levels are associated with atherosclerosis, arterial calcification, and heart failure, thus indicating their involvement in cardiac remodeling and vascular pathology; OPG regulates calcification and vascular homeostasis by restricting the transdifferentiation of vascular smooth muscle cells into osteogenic phenotypes; OPG expression is aberrant in illnesses posing cardiovascular risk, such as aortic valve stenosis, chronic renal disease, and diabetes; OPG interacts with inflammatory and apoptotic mediators, including RANKL and TRAIL, in signaling pathways linking bone metabolism, inflammation, and vascular dysfunction; Myocardial infarction, left ventricular remodeling, and mortality are associated with elevated circulating OPG and altered OPG/TRAIL ratios ²⁾

• normal gain in bone density in early life, plateau ~30yr old then gradual fall, especially postmenopausal women partly due to lack of oestrogens and exacerbated by inactivity, low Ca intake, low fluoride intake, space flight where no gravity (disuse ostoporosis)
• see osteoporosis