Osteoporosis Flashcards
Pathophysiology of osteoporosis
-Imbalance between bone resorption and formation
=Osteocytes master regulators of bone metabolism (RANKL stimulates osteoclast, sclerostin inhibits osteoblasts)
=Thinning of bones
Definition of osteoporosis
A disease characterised by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and increased fracture risk
=Individuals with BMD >2.5 SD below the young normal mean (T score)
Clinical presentation of osteoporosis
-Fragility fractures
=Fall from standing height or less
-Vertebral fractures
=Acute or chronic back pain
=Height loss
-Low bone density does not cause symptoms
Differential diagnosis of acute vertebral fracture
-Myocardial infarction (pain radiate to anterior chest wall)
-Aortic dissection
-Pulmonary embolus
-Disc prolapse
-Osteoarthritis
Pathogenesis of osteoporotic fractures
-Bone component:
=Genetics (Caucasian and Asian)
=Diet with sedentary lifestyle
=Smoking
=Steroids
=Menopause (premature?)
-Falls component:
=Muscle weakness
=Poor balance
=Poor vision
=Hypotension
=Sedatives
Risk factors/ regulators of bone loss
-Sex hormone deficiency/ female sex
-Advancing age
-Genetics
-Diet, with alcohol excess, smoking, and low BMI
-Immobility with history of parental hip fracture
-Disease: RA, endocrine, multiple myeloma, IBD, malabsorption, CKD
-Drugs
=Corticosteroids
=Aromatase inhibitors (breast cancer)
=Glitazones
=PPI
=Long term heparin therapy
=Antiepileptics and SSRIs
Diagnosis of osteoporosis
-Fracture risk assessment
-Dual Energy X-ray Absorptiometry (DEXA) if score >10%
-FBC, sedimentation rate, CRP, calcium, LFT, thyroid, bone profile= secondary causes
Indications for DEXA Scotland
-Fragility fractures aged > 50 yrs
=Fracture liaison service usually organises DEXA
=Women 75+ may not be required if inappropriate or unfeasible
-Suspected vertebral fracture
=Height loss, back pain
-Glucocorticoids
=Prednisolone >7.5mg > 3months
-Ten year fracture risk >10% (SIGN 142)
=Q-Fracture or FRAX
Principles of management of the patient with an acute fracture
-Initial assessment and resuscitation
=Airway, breathing, circulation, disability, exposure and environment
-Analgesia
-Wound management
-Fracture fixation or immobilisation
Management of an acute vertebral fracture
-Analgesia
=Strong opiates (MST, oxycodone, fentanyl)
=Lidocaine patch (unlicensed)
=Anti-neuropathic agents, compound analgesics, NSAID
-Neurosurgery
=Indicated for spinal cord compression (very rare)
Approaches to the prevention of Osteoporotic fractures
-Lifestyle Modification
=Diet, Exercise
=Smoking, Alcohol
-Non drug treatments
=Physical therapy to improve balance and muscle strength
=Falls prevention
-Drug treatments that affect bone
Drug treatments options for osteoporosis
Antiresorptive
-Bisphosphonates
=Alendronic acid (all patients: first line)
=Risedronate/ etidronate (2nd line if alendronate GI upset)
=Zoledronic acid (reduces risk of fracture in postmenopausal OP)
-Denosumab (keep going long term/ start bisphosphonate if stopped, targets RANKL, strictest criteria)
-HRT
Anabolic (stimulate osteoblasts)
-Strontium ranelate or raloxifene (oestrogen receptor modulator) if bisphosphonates not tolerated (strict criteria)
-PTH (enhances bone formation)
-Romosozumab (targets sclerostin)
Supplements
-Calcium and Vit D (elderly institutionalised not community dwelling)
-Vit D alone
When should you start treatment for Osteoporosis?
-Men or women with low trauma vertebral fractures (these patients will usually be offered an appointment at the osteoporosis clinic)
-Men with a -score <-2.5 at either spine or hip on DEXA where the 10-year fracture risk is >10%
-Low trauma hip fracture
=Zoledronic acid
-Postmenopausal women with a T-score <-2.5 at either spine or hip on DEXA where the 10-year fracture risk is >10%
-Postmenopausal women age ≥65 with a fragility fracture may be offered IV zoledronate if T-score <-1 and > -2.5at either spine or hip on DEXA based on most recent SIGN guideline update.
=Zoledronic acid
-Long-term glucocorticoids
=Patients on >7.5mg prednisolone for >3 months in whom the T-score on DEXA is <-1.5 and the 10 year fracture risk is >10
-Evidence for treating patients with high fracture risk in the absence of BMD is limited
Mechanism of bisphosphonate action
-OH group enhances mineral binding
-Nitrogen side chain increases potency and affects mineral binding
-Phosphonate groups bind to calcium and target drugs to bone
=Bisphosphonate adheres to bone surface
=Bone mineralisation increases, density increases, tissue mass remains static
=Bisphosphonate is released within osteoclast causing cell death
=Osteoclasts resorb bone containing bisphosphonate
Adverse effects of bisphosphonates
-Common
=Upper GI upset with oral medication (~5%)
=Transient Flu like illness with IV therapy (~25%)
-Rare
=Hypocalcaemia (IV therapy, give calcium and vit D)
=Bone and joint pain
-Very rare
=Osteonecrosis of the jaw (ONJ)
=Atypical femoral fracture (AFF)
=Atrial Fibrillation – zoledronic acid
=Uveitis
