MSK - metabolic bone disease Flashcards
list the common conditions that can lead to secondary osteoporosis
•Cushing’s syndrome or exogenous corticosteroids (eg > 5 mg/day for > 3 mths)
•Excessive alcohol use (> 2 units or 18 g/d)
•Smoking
•Malabsorption (coeliac, Inflammatory Bowel Disease)
•Primary or secondary hypogonadism
–e.g. associated with medications (corticosteroids, opioids, androgen deprivation therapy for prostate cancer, aromatase therapy for breast cancer)
Less common:
•Low BMI, high BMI (lack of/excessive exercise)
describe the clinical features of vitamin D deficiency and osteoporosis
• commonly asymptomatic
• height loss due to collapsed vertebrae
• fractures: most commonly in hip, vertebrae, humerus and wrist
- fragility fractures: fracture with fall from standing height
- Dowager’s hump: collapse fracture of vertebral bodies in mid-dorsal region
- x-ray: vertebral compression and crush fractures, wedge fractures, “codfishing” sign
(weakening of subchondral plates and expansion of intervertebral discs)
• pain, especially backache, associated with fractures
25-OH-Vitamin D level should only be measured after 3-4 mo of adequate supplementation and should not be repeated if an optimal level ≥75 nmol/L is achieved
interpret bone density tests (Z-score & T-score) tests and diagnose osteopenia or osteoporosis according to WHO criteria
Dual energy x-ray absorptiometry (DEXA): gold standard for measuring bone mineral density:
•Z-score: accounts for the patient’s AGE, sex and ethnicity (
calculate absolute fracture risk
Multiple methods:
- FRAX by WHO
- Garvan Tool
FRAX includes:
- clinical risk factors, bone mineral density, and country-specific fracture and mortality data to quantify a patient’s 10-year probability of a hip or major osteoporotic fracture.
- risk factors comprise of femoral neck bone mineral density, prior fractures, parental hip fracture history, age, gender, body mass index, ethnicity, smoking, alcohol use, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis.
FRAX was developed by the WHO to be applicable to both postmenopausal women and men aged 40 to 90 years
interpret radiological imaging tests to diagnose vertebral and other fractures
- lateral beak on XR suggests a stress fracture
- dual energy x-ray absorptiometry (DXA)
- BMT T-score
- Bone turnover markers: Resorption, serum b-CTX (bone resorption marker), Formation, P1NP (bone formation marker)
What are the preventative strategies used to prevent the onset of osteoporosis?
- Diet: Elemental calcium 1000-1200 mg/d; Vit D 1000 IU/d
- Exercise: 3x30 min weight-bearing exercises/wk
- Cessation of smoking, reduce caffeine intake
- Stop/avoid osteoporosis-inducing medications
describe the different therapeutic agents used to treat osteoporosis
- Hormone Replacement therapy (mostly women only). Limit factors stimulating bone resorption
- Raloxifene (women only)
- Bisphosphonates: inhibit osteoclast formation & increase osteoclast apoptosis
•Alendronate
•Risedronate
•Zoledronate - Teriparatide
- Denosumab: binds to RankL
- (Strontium): activates osteoblast & inhibit osteoclast formation
explain how to monitor treatment responses to osteoporosis therapy and how to use second-line treatments for osteoporosis when first-line treatments fail
First line:
- Alendronate, Risedronate, Zoledronic acid (Bisphosphonate)
- Denosumab (RANKL inhibitors)
- Raloxifene (SERM for post-menopausal women)
- HRT (for post menopausal women)
Second line:
- Etidronate (bisphosphonate)
- Calcitonin (osteoclast receptor binding)
Monitor with:
beta-CTX, P1NP, BMD (bone mineral density)
If BMD increases to >T -2.5 at femoral neck after 3-5 years, a “drug holiday” can be considered, but only if the patient is monitored for any subsequent bone loss
How much height loss is significant?
> =3cm
Likely due to loss of height of vertebra(e) or intervertebral disc spaces
What are risk factors for osteoporosis?
- Low exercise levels
- Smoker (40 pack years)
- Co-morbidities (Rheumatoid arthritis etc)
- Poor nutrition, low calcium intake
- At risk of Vitamin D insufficiency/deficiency
- Prolonged amenorrhoea in younger years
- Post-meonpausal at age 50 y.o.
–previous fracture history
–family history of fracture/ osteoporosis
–No previous/current therapies for postmenopausal osteoporosis
What is P1NP in terms of bone health?
Bone formation marker
•Procollagen type 1 propeptides
•Cleared by liver endothelial cells
What is CTX in terms of bone health?
Bone resorption marker •Cleaved during bone resorption •Diurnal variation (8-9:30am) •Fasting •Cleared by kidneys
Choice of therapy in osteoporosis therapy in CKD
- Raloxifene (vertebral fracture risk protection only)
- Oral alendronate (weekly tablet)
- Oral risedronate (weekly or monthly tablet)
- Six monthly subcutaneous denosumab injections
Bisphosphonates must be used with hypocalcaemia precaution in CKD stage 4-5.
Describe some side effects of long term bisphosphonate therapy
- Atypical femoral fracture (with prolonged use)
- Osteonecrosis of the jaw (esp for IV bisphophonate)
List (5) causes of fractures in chronic kidney disease
- Osteoporosis
- Osteomalacia
- Hyperparathyroidism
- Adynamic bone disease
- Post-transplantation (steroid, calcineurin inhibitors)
