Metabolic Bone Disease Flashcards
What is osteoporosis?
- complex skeletal disease characterised by low bone density + micro-architectural defects in bone tissue
- resulting in increased bone fragility + susceptibility to fracture
- may be primary (age-related) or secondary to another condition/drug
Advancing age and female sex are significant risk factors for osteoporosis. Prevalence of osteoporosis increases from 2% at 50 years to more than 25% at 80 years in women.
What are the risk factors for osteoporosis?
SHATTERED
- Steroid use of >5mg/d of prednisolone
- Hyperthyroidism / Hyperparathyroidism / Hypercalciuria
- Alcohol + tobacco use
- Thin (BMI <18.5)
- Testosterone reduced (eg. antiandrogen Ca prostate)
- Early menopause
- Renal or liver failure
- Erosive/inflammatory bone disease (myeloma, RA)
- Dietary reduced Ca/malabsorption; DMT1
What are the clinical features of osteoporosis?
- Asymptomatic
- Predisposes pts to be at higher risk of fragility fractures:
- crush fractures of vertebrae
- colle’s fracture
- neck of femur fracture
What is the pathophysiology of osteoporosis?
- Bone is an active tissue that constantly remodels in response to mechanical stresses + hormonal changes
- Osteoclasts resorb bone matrix + express RANK receptors
-
Osteoblasts build new bone matrix, which undergoes mineralisation
- RANK ligand (RANKL) expressed on osteoblasts which bind to RANK receptors on osteoclasts to facilitate osteoclast formation, function + differentiation
-
OPG secreted by osteoblasts + naturally inhibits RANKL-induced activation of RANK
- keeps bone resorption in balance; however, in post-menopausal women w/ oestrogen deficiency, overexpression of RANKL activity overrides natural inhibitory activity of OPD
To assess the actual bone mineral density a dual-energy X-ray absorptiometry (DEXA) scan is used. The DEXA scan looks at the hip and lumbar spine. If either have a T score of < -2.5 then treatment is recommended.
What is meant by the T score?
- T-score is number of standard deviations the bone mineral density is from the youthful average
- each decrease of 1 SD in bone mineral density equals roughly a 2.6 fold increase in risk of hip fracture
- T score of -1.0 means bone mass is of one SD below that of young reference population
- Z score is adjusted for age, gender + ethnicity
What is FRAX?
- Assessment tool that estimates the 10-year risk of fragility fracture
- Valid for patients aged 40-90 years
- Can be done before or after DEXA scan + gives different results for each:
-
WITHOUT a bone mineral density:
- low risk → reassure + give lifestyle advice
- intermediate risk → offer BMD test
- high risk → offer bone protection treatment
-
WITH a bone mineral density:
- low-risk → reassure
- intermediate risk → consider treatment
- high risk → strongly recommend treatment
What is the conservative management of osteoporosis?
- quit smoking + reduce alcohol consumption
- weight-bearing exercise may increase bone mineral density
- balance exercises such as tai chi reduce risk of falls
- home-based fall-prevention programme
What is the 1st line medical management of osteoporosis?
- Bisphosphonates → Alendronic acid (10mg/d)
- ~25% pts cannot tolerate alendronate due to upper GI problems
- These pts should be offered risedronate or etidronate
- Tell pts to swallow pills w/ plenty of water while remaining upright for >30min + wait 30min before eating or taking other drugs
- SEs: photosensitivity / GI upset / oeseophageal ulcers / rarely jaw osteonecrosis
What is the role of vitamin D + calcium in management of osteoporosis?
- rarely used alone for prophylaxis
- questionable efficacy + some evidence of small inc CV risk
- offer if evidence of deficiency
What is the role of raloxifene in osteoporosis management?
- selective oestrogen receptor modulator (SERM)
- shown to prevent bone loss and to reduce risk of vertebral fractures
- has not yet been shown to reduce risk of non-vertebral fractures
- may worsen menopausal symptoms
- inc risk of thromboembolic events
- may reduce risk of breast cancer
What is the role of denosumab in osteoporosis management?
- human monoclonal antibody
- inhibits RANK ligand → inhibits maturation of osteoclasts
- given as single subcut injection every 6 months
- initial trial data suggests it is effective + well-tolerated
Ostoemalacia is when there is a normal amount of bone but its mineral content is low. Rickets is the result if this process occurs during the period of bone growth. Osteomalacia is the result if it occurs after fusion of the epiphyses.
What are the clinical features of rickets and osteomalacia?
-
RICKETS
- Growth faltering
- Hypotonia
- Apathy in infants
- Once walking: knocking knees, bow-legged and deformities of metaphyseal-epiphyseal junction
- Features of hypocalcaemia often mild
-
OSTEOMALACIA
- Bone pain + tenderness
- Fractures (eg. femoral neck)
- Proximal myopathy - waddling gait
What are the causes of osteomalacia?
- Vit D deficiency
- Vit D resistance
- Renal osteodystrophy
- Drug-induced (anticonvulsants)
- Liver disease
Is all linked to hydroxylation of Vit D and enzymes involved
What investigations are done for osteomalacia?
- Bloods → reduced Ca + phosphate / inc ALP / inc PTH / reduced 25OH-Vit D (unless Vit D resistance)
-
X-ray
- children → cupped, ragged metaphyseal surfaces
- adults → translucent bands (Looser’s zones or pseudofractures)
What is the treatment of osteomalacia?
- dietary insufficiency → give calcium D3 tablet 12hr PO
- malabsorption or hepatic disease → Vit D2 up to 40,000U daily
- renal disease or vit D resistance → alfacalcidol or calcitriol and adjust dose according to plasma Ca as risk of hypercalcaemia
