Causes of osteoporosis
- Menopause - lack of estrogen
- Hypogonadism
- Vitamin D deficiency
- Hyperthyroidism
- Coeliac disease
- Primary hyperparathyroidism
- Monoclonal gammopathy of uncertain significance (MGUS)
Diagnostic criteria
- Bone Mineral Density using DEXA scan - T <-2.5
- Fragility fracture after the age of 50
Peak bone mass is achieved at what age
40-50
Options for drugs in Osteoporosis
- Antiresorptive
- Bisphosphantes- Alendronate
- Selective oestrogen receptor modulator - Tamoxifen, Raloxifen
- Oestrogen
- Calcitonin
- RANKL inhibitor - Donesumab
- Anabolic
- PTH
Examples of anti resorptive drugs used in osteoporosis
- Bisphosphonates : inhibits osteoclast - apoptosis . Alendronate, rerisdronate, etidronate, pamidronate, zolendronate
- Raloxifene - estrogen receptor modulator (also called SERMS, selective estrogen)
- Denosumab - binds to RANKL
Anabolic agent used in osteoporosis
Teriparatide - synthetic parathyroid hormone increases osteoblastic activity
DDx for osteoporosis
- Osteopenia
- Multiple myeloma
- Osteomalacia
- Chronic kidney disease
- Primary hyperparathyroidism
- Metastatic bone malignancy
- Vertebral deformities
- Osteogenesis imperfecta
- Hypogonadism
- Cushing’s syndrome
- Rhematoid arthritis
- Mastocytosis
Two main factors that determine risk of osteoporosis
- Peak bone mass
- genetics
- ca, diet, exercise
- Rate of bone loss
Risk factors for low bone mass
Non-modifiable
- Age
- Race
- Female
- Early menopause
- Slender build
- Family history
Modifiable
- Low Ca intake
- Low vit D intake
- Oestrogen deficiencyy
- Sedentry lifestyle
- Smoking
- Alcohol
- Caffeine
- Medication
Bone mass and quality in Osteoporosis
- Loss of bone mass
- Reduction in bone quality
- loss of horizontal struts
- loss of connectivity
- conversion of trabecular plates to rods
- Resorption pits are “stress concentrators”
- Unfavorable geometry
Definition of osteoporosis
systemic skeletal disease chracterised by low bone mass and micro-architectural deterioriation of bone tissue resulting in increase fragility and risk of fracture
Risk factors for Osteoporotic fracture
Major
- Personal history of fracture as an adult
- history of fragility fracture in 1st degree relative
- low body weight
- current cigarette smoking
- >3 months of oral corticosteriod use
Additional
- Estrogen deficiency at an early age
- dementia
- excessive alcohol use
- recent falls
- inadequate physical activity
- poor health/fragility
- impaired vision
- lifelong low Ca intake
Investigations for suspected osteoporosis
- X-ray - fracture
- Bloods
- Bone turnover markers : Ca, PO4, ALP, Osteocalcin (urine = increased turnover), urine hydroxyproline
- Bone pathogenic marker : TSH, PTH, Ca, PO4, EUC, Cr, Testosterone, Vitamin D, Serum and urine electrophoresis
- Bone scan - detects osteoblastic activity + new fracture, pagets and metastatic lesions
- MRI - new fracture
- BMD diagnosis
- Bone Biopsy
- Bone u/s - not standardised
What is the difference between T-score and Z-score in DXA scan
T score = compared to mean peak bone mass, what is desirable
Z score = compared to age and gender matched controls, what is expected, if bone mass is unusually low
Important risk factors in Fracture risk calculations
Age
BMD
Hx of prior fractures
Difference between the trabecular bone in glucocorticoid induced osteoporosis and osteoporosis
GIOP = generalised thinning of trabeculae
Postmenopausal osteoporosis = breakage of trabeculae
Treatment for glucocorticoid induced osteoporosis (GIOP)
- Reduce or replace steriod treatment
- Vit D, Calcium
- Bisphosphanates
Definition of osteomalacia
Systemic skeletal disorder of mineralisation of newly formed organic matrix
In children results in ricket’s
What is required for normal bone mineralisation
- Normal ca and PO4 concentration
- Presence of alkaline phosphatae and mature bone matrix
- Absence of inhibitors - bisphosphonate and aluminium
Causes of osteomalacia
- Vitamin D abnormality
- D defciency
- liver disease
- renal disease
- 1 a- hydroxylase deficiency
- vit d resistance
- Hypophosphateamia
- x-linked hypophosphatemia rickets
- autosomal dominant hypophosphatemic rickets
- autosomal recessive hypophosphatemic rickets
- excessive klotho
- oncogenic osteomalacia
- Disorder of bone matrix - hypophosphatasia
- Inhibitors of mineralisation
- Bisphosphonate
- aluminum
- Toxicities
- Fluoride
- etidronate
- perenteral alunium
- imatinad
- Acidosis
Investigations (findings) of osteomalacia
- Low Vit D
- Hypocalcaemia
- Hypophosphataemia
- High PTH
- Low BMD
Treatment of osteomalacia
- Reversible
- Cod liver oils, fish, egg, meat
- Vit D exposure
Characteristics of Osteitis Deformans
- Focal skeletal disorder
- Accelerated bone turnover
- disorganised bone formation
- high BMD
- High bone turnover - ALP, urinary hydroxyproline
Definition of osteodystrophy
Combination of
- Osteoporosis
- osteomalacia
- adynamic boen disease - aluminum toxicity resulting in low bone turnover
Occurs in chronic renal failure or ialysis patients
