Block 6: thyroid, osteomalacia Flashcards
Markers of bone activity
- Bone resorption (Osteoclast activity): N-terminal telopeptide of type I collagen (NTX), C-terminal telopeptide of type I collagen (CTX), Hydroxyproline
- Bone formation (Osteoblast activity); Alkaline phosphatase (bone specific), Osteocalcin, N-terminal propeptide of type I procollagen (P1NP
Bone mineral density: BMD
- Measured by dual X-ray absorptiometry (DXA) at hip and spine (g/cm2): done for a particular area
- Z-score: BMD compared to age matched population
- T-score: BMD compared to race and sex matched peak adult BMD- young adult
- Both expressed as standard deviations from population mean
Osteoporosis
- Common problem in elderly population
- Hip fracture commonly leads to death
- Defined in several ways: Clinically- presence of low-impact fracture: Hip, Lumbar spine, Colles. Radiographically- presence of low bone mineral density
- Reduced bone mass
- Normal biochemistry
Fragility fracture and deformity
NOF, vertebral collapse, wrist, vertebral. Vertebral fractures cause loss of height and thoracic kyphosis. Fragility fracture is from standing height or less
T score criteria
- Fragility fracture defines ‘Established osteoporosis’: not reliant on bone density
- T score of -2.5 or less is WHO definition of osteoporosis
- T score of -1 to -2.5 defines osteopenia
Factors affecting bone mass and loss
- Increased: gets higher between 0 and 30, exercise, increased calcium intake
- Worse: Menopause, drugs, disease, iron deficiency, immobility
Risk factors for osteoporosis
- Low weight (<55kg), tall height (>5’7”)
- Smoking & Alcohol use
- Medication use (steroids)
- Premature menopause, hypogonadism
- Low calcium intake
- Family History
- Ethnic background: South asian
Secondary osteoporosis
- Malabsorption, Hepatic or Renal disease
- Endocrine problem: Hypogonadism, thyrotoxicosis, hyperparathyroidism, Cushings
- Drugs: Steroids, anticonvulsants, heparin
- Others: Rheumatoid arthritis, Osteogenesis imperfecta, Systemic mastocytosis, Immobilization, weightlessness
Osteopenia treatment- risk stratifying to prevent osteoporosis
- Increase Calcium intake (>1200 mg/day): diet (dairy or green cabbages) or medication
- Increase Vitamin D intake (>800 U or 20mcg /day): Cholecalciferol
- “Life-style” - Weight-bearing exercise
- These measures can also be used in osteoporosis
Treatment for osteoporosis
- Bisphosphonates (Alendronate: oral weekly or Zolendronic acid: IV annually)
- Denosumab (anti-RANKL mAb): SC every two years
- Hormone replacement therapy: Menopause, hypogonadism, use before vitamin D and calcium replacement
- Selective estrogen receptor modifiers (SERM): Roloxifene, used in milder osteoporosis
- PTH injections: help bone to growth. Teriperatide daily injection
- Romosozumab- anti-sclerostin mAb: if failed to improve bone density or fracture after Bisphosphonate course. Help bone to grow
Investigations for osteoporosis and how to take Bisphosphonates
- FRAX score: to determine whether to treat, shows risk of any major fracture
- BMD
Taking Bisphosphonates: Need to be standing up (can cause oesophagitis)
Sources of vitamin D
- Sunlight (UVB) on exposed skin. 1,25- Dihydroxy vit.D3 is the active form. Sun cream stops vitamin D production.
- Oily fish: Salmon, trout, mackerel, tuna, anchovy, sardine, pilchard etc.
- Small amount in meat, egg yolk
- Mushrooms (grown outdoors)
- A persons average levels of vitamin D change with the season
Vitamin D levels: osteomalacia
- > 75: optimal, healthy
- 50-75: adequate vitamin D, Healthy, offer lifestyle advice
- 25-50: insufficient vitamin D, associated with disease risk, supplement with vit D
- <25: deficient, rickets and osteomalacia, treat with high dose vit D
pathophysiology of osteomalacia
- Mineralisation defect in the bone: lack of vitamin D impairs calcium absorption. Reduced mineralisation of osteoid. More unmineralized bone so they bend. Also low phosphate
- Rickets: childhood disease where you can see bends in bone because they are incompletely mineralised. In osteomalacia you don’t see the bent bones as they are already grown
Rickets/osteomalacia
- Low serum 25-OH vit D
- Elevated PTH
- Elevated alkaline phosphatase
- Hypocalcaemia, hypophosphataemia
- Due to: Lack of sunlight +/- dietary vitamin D, Drugs, Dietary lack of calcium/ phosphate deficiency, Renal or Hepatic disease (lack of activation of vitamin D)
Drug induced osteomalacia
- Anticonvulsants (induce hepatic D metabolism- more burnt off): should prophylactically receive vitamin D supplements
- Colestyramine/colsevalam (malabsorption)
- Bariatric surgery
- Fat malabsorption (pancreatic insufficiency)
Features of osteomalacia
- Symptoms: Weakness, myalgia, bone pain, tetany, paraesthesia, dental abnormalities, fractures
- Skeletal: bowing deformities, spinal deformities (kyphosis or scoliosis)
- Rickets (osteomalacia in children): Bowing of legs, knock knees, craniotabes (can indent skull).
X-ray appearance of osteomalacia
- Cupped epiphyses,
- Loosers zones: bone under mineralisation- pseudo fractures, present as radiolucent band
- Rachitic rosary (enlarged costochondral junctions on ribs)
Treatment for osteomalacia
- Colecalciferol: 20,000 units oral twice weekly for 12 weeks. Maintainance of 800-1000 U/d forever
- Ergocalciferol: Same doses, Suitable for vegetarians
- Suitable sun exposure: if European descent 20-30 minutes of sunlight on arms and face at midday