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1.4: An Embarassing Fall, X-ray, Physical examination, Depression, lives…

- - - - Less cholecalciferol (vit D3) formed
        
        in liver, hydroxyl group added
        
        Less 25-hydroxyvitamin D3 formed
        
        in kidney, hydroxyl group added
        
        Less 1,25-dihydroxyvitamin D3 formed
        
        INTESTINES: LESS Ca & PO4 absorption
        
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        Stable form, measured to assess vit D levels
- - - - Sclerostin binds to LRP5/6 receptor on osteoblasts, prevcenting formation of Frizzled complex
        
        Phosphorylation of GSK-3beta, which phosphorylates and ubiquitinates beta-catenin
        
        Beta-catenin undergoes proteasome degradation, preventing translocation to the nucleus and expression of proteins involved in bone formation
        
        Decreased bone formation
- - - - Kidneys: PTH-1-receptor stimulated
        
        Enhances renal reabsorption of Ca2+
        
        Enhances renal excretion of Phosphate
      - Bone: PTH-1-receptor on osteoblast stimulated
        
        RANKL-receptor on osteoblast binds RANK on pre-osteoclasts
        
        Fusion of pre-osteoclasts to form active osteoclasts
- - - - Ongoing Management
        
        1st line: bisphosphonates (po/iv)
        
        Attach to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing active resorption, decrease bone resorption by inhibiting osteoclasts
        
        Risendronate and alendorate are oral weekly tablets (poor persistence, but consistency required for long-term management)
        
        Zolendronic acid is a yearly IV infusion (5mg) (better compliance)
        
        Other options include etidronate and ibandronate
        
        Denosumab (only in elderly)
        
        Human monoclonal antibody binding RANKL, preventing activation of RANK receptor
        
        results in decreased formation and activity of osteoclasts
        
        Reduce bone resorption
        
        60mg subcutaneous injection every 6 months
        
        PTH agonist: teriparatide
        
        intermittent doses of PTH analogue
        
        Promotes bone formation and increases BMD
        
        intermittent dosing to prevent RANK activation which normally increases osteoclast activity
        
        osteoblast activation to increase bone formation without increase of osteoclast activity
        
        Daily subcutaneous injection
        
        Exercise
        
        Osteocytes respond to increased dynamic loading
        
        Increases in bone density
        
        Increase in muscle mass
        
        HRT
        
        Normally used for menopausal symptom relief that is caused by reduced endogenous oestrogen production
        
        Ideally not used in patients with a family history of breast cancer
        
        Romosozumab
        
        anti-sclerostin mAb
        
        increased bone formation and decreased bone resorption in postmenopausal women
        
        Will be available in Australia in April 2021
        
        Ca2+ and vit D supplementation
        
        Only effective in patients with deficiencies, not useful in excess amounts
        
        Lifestyle changes
        
        Stop smoking
        
        Hip protectors
      - Immediate management
        
        Oxygen 4L per minute via nasal prongs
        
        In-dwelling catheter
        
        Morphine 5mg intramuscular, femoral nerve block with local anaesthesia
        
        Surgery
        
        Pre-operative assessment
        
        Check renal function
        
        Respiratory risk (CXR, ABG)
        
        Anaesthetic review (local vs general)
        
        DVT prophylaxis
        
        Procedure
        
        Compression hip screw
        
        Post-operative care
        
        Mobilisation
        
        Rehabilitation
- - - - Increased bone resorption with insufficient increase in bone formation
        
        Decreased bone mass and BMD and microarchitectural deterioration of bone (loss of trabeculae, trabecular thickening, cortical thinning and cortical porosity)
        
        OSTEOPOROSIS
        
        Laboratory testing
        
        FBC
        
        Normal WCC and platelet levels
        
        1 more item...
        
        Low MCV & MCH
        
        1 more item...
        
        Midstream urine
        
        no growth
        
        1 more item...
- - - - Demineralisation of bone and breakdown of collagen I, release of Ca and PO4
        
        Increased bone resorption