Osteoporosis Flashcards
List some DDx for a pathological fracture?
• Metabolic o Osteoporosis o Osteomalacia o Paget’s disease o Renal osteodystrophy o Hyperparathyroidism o Hyper/hypothyroidism o Cushing’s disease • Neoplastic o Primary - Osteosarcoma - Multiple myeloma - Leukaemia - Lymphoma o Secondary - Osteolytic lesions from bone mets (CRC, breast) • Infective- osteomyelitis • Drug-induced: steroid use, anticonvulsants • Nutritional- vit D, calcium deficit • Trauma
What are some risk factors for osteoporosis?
o Increased age (post-menopausal) o Female o Caucasian o Previous pathological # o Low BMI o Smoking o Excess ETOH o Drugs- chronic steroid use o Nutritional deficiency- vit D and Ca o Coeliac disease o Endocrine (hyper/ hypothyroidism, hyperparathyroidism) o Renal disease
List the risk factors for falls?
Risk factors for falls (DAME mnemonic): D- drugs (e.g. steroids) A- age-related changes M- medical conditions E- environment
What investigations would you order for a suspected hip fracture?
Diagnostic: - X-ray of hip - DEXA Bedside: - ECG - BSL - Postural BP Lab: - FBC - CRP/ESR - UEC - CMP (Ca and PO4) - PTH - LTFs - TFTs - Vit D - Serum/urine electrophoresis - Serum/urine hydroxyproline (Paget) - bone turnover markers (N-telopeptide (NTX) and carboxy-terminal collagen crosslinks (CTX)) Imaging: - bone scan
How do you determine bone mineral density?
Dual energy x-ray absorption (DEXA)- determines bone mineral density (BMD)
o Osteoporosis: <2.5 standard deviations below young adult mean
o Osteopenia: -2.5 to -1 SD
o Indications: women >65yo, post-menopausal women, women <65yo w >1 risk factor for #, men with risk factors for #
o Sites: femoral neck, lumbar spine
o Control: compared w bone density of health 30yo
o Repeat 3-5 years if normal and no risk factors
What are the BMD T scores and Z scores for diagnosis?
• T score: number of SDs the pt’s BMD is from the mean (of sex-matched healthy 30yo)
o Normal= >-1
o Osteopenia= -2.5 to -1.5
o Osteoporosis=
Describe the pathogenesis of osteoporosis?
• Path: trabecular (spongy) and cortical bone lose mass and interconnections, despite normal bone mineralization and lab values (serum Ca2+ and PO4 3-)
• Normally: osteoclasts resorb bone and osteoblasts replace bone -> remodelling orchestrated by osteocytes
• Osteoporosis: over supply of osteoclasts relative to need for remodelling OR undersupply of osteoblasts relative to need for cavity repair
o Age- progressive reduction in replicative and matrix production acitivties of osteoblasts
o Hormones- decline in oestrogen -> increased cytokine production (esp IL1, IL6, TNF) -> stimulate RANK-RANKL activity -> suppress Osteoprotegerin (OPG) (osteoclastogenesis inhibitor) -> more osteoclasts produced -> accelerated cortical bone and trabeccular bone loss
What histological changes might you see in osteoporosis?
- cortices thinned
- dilated Haversian canals
- thinned trabeculae
List some primary causes of osteoporosis?
Primary:
o Nutritional (decreased Vit D and Ca)
o Decreased oestrogen
o Low levels of weight-bearing exercise
o Osteomalacia- bone softening due to Vit D or Ca deficiency -> more collagen than minerals in bone osteoid
o Paget’s disease: increased but structurally poor bone deposition
List some secondary causes of osteoporosis?
Secondary:
o Endocrine- hyperparathyroidism, hypo/hyperthyroidism, hypogonadism, pituitary tumour, T1DM, Addison’s disease, Cushing’s disease
o GIT- malnutrition, malabsorption, hepatitic insufficiency, Vit C and D insufficiency
o Renal osteodystrophy
o Drugs- chronic corticosteroids, anticoags, anticonvulsants, ETOH, chemo
o Neoplasia
- Primary- osteosarcoma, osteomyeloma, MM
- Secondary- breast, prostate, lung, RCC, melanoma
o Congenital- osteogenesis imperfecta, Collgen type 1 deficiency, Marfans syndrome, haemochromatosis, hypohosphatasia
o Immobilisation
o Anaemia
What are the non-pharmacological treatments for osteoporosis?
• Diet
o Adequate calorie intake
o Increase Ca intake, esp <30yo (1,200mg daily)
o Preventing Vit D deficiency: sunlight, Vit D tablets (800IU daily)
• Smoking cessation (accelerates bone loss)
• Weight bearing exercise -> strengthens muscles and increases bone deposition (>30mins, x3/week)
• Minimise immobility
• Falls prevention- improve vision, medication review, assess household, walking aids, hip protectors
When is pharmacological treatment of osteoporosis indicated and what is the regimen?
Indicated in:
o Post menopasual women w estabolished osteoporosis or prev pathological # (hip, vertebral)
o High risk post menopausal women (T between -1 and -2.5)
Regimen: o 1st line: anti-resorptive agent - Bisphosphonates - Anti-RANKL Ab (Denosumab) o 2nd line: hormonal agent - SERMS (Tamoxifen) - PTH (Teriparatide) - HRT - Calcitonin
Describe the MA of Bisphosphonates? Give an example.
Bisphosphonates (e.g. Alendronate)
o MA: attach to hydroxyapatitie binding sites on bony surfaces -> osteoclasts resorb bone impregnated with Bisphosphonate
-> impairs osteoclast ability to adhere to bony surface AND to produce protons needed for continued bone resorption
o Also promote osteoclast apoptosis AND reduced osteoclast progenitor development -> reducing osteoclast activity
Dose: oral Alendronate (70mg PO weekly, up right 30mins after, empty stomach) OR IV Zoledronic acid (6/12)
Describe the SE and CI of Bisphosphonates?
o SE: uncommon, hypocalcaemia, abdo pain, myalgia, nausea, dyspepsia, jaw osteonecrosis (rare)
o CI: low Ca, oesophageal disorders, CKD
Describe the MA of Anti-RANKL antibodies? Give an example.
Anti-RANKL antibody (e.g. Denosumab)
o MA: human monoclonal antibody against RANK-ligand -> prevents RANK receptor activation (mimics osteoprotegerin)
-> prevents osteoclast development -> less bone resorption
Dose: SC injection 6/12
