Osteoporosis Flashcards
What are the clinical manifestations of osteoporosis?
No clinical manifestations until a fracture
Common sites of fracture:
- Vertebral compression #
- Hip # (neck of femur, intertronchanteric)
- Distal Radius Fracture (e.g. Colle’s #)
- Humoral Head #
How is osteoporosis diagnosed?
Fragility fracture, ANY FRACTURE that occurs from standing height or less, without major trauma e.g. vehicle accident OR
T-score ≤ -2.5 standard deviations (SD) at any site based upon bone mineral density (BMD) measurement by dual-energy x-ray absorptiometry (DEXA)
How do you interpret the T scores on DEXA scans?
Compares pt’s results to a healthy 20YO person matched for race and sex
Used to determine Osteoporosis & Osteopenia for post-menopausal women and men >50YO
- Osteoporosis ≤-2.5
- Osteopenia = -1 ~ -2.4
How do you interpret the Z scores on DEXA scans?
Compares pt’s results to those of an age-matched population that also is matched for race and sex – aka compared to peers w same age, race and sex
Used to determine Osteoporosis only for pre-menopausal women and men <50YO
Osteoporosis ≤-2.0 (for pre-menopausal women and younger men)
Z score is not used to determine osteopenia! Hence if a younger male / pre-menopausal woman has NO osteoporosis (Z score <2.0), they are also considered to have NO osteopenia
What are the primary causes of osteoporosis?
Post-menopausal
- Increased bone resorption due to withdrawal of estrogen which restricts osteoclastic activity
- Accelerated rate of bone loss
Senile (aka old age): Gradual slowdown in osteoblastic activity
What are secondary causes of osteoporosis ?
Endocrine causes
- Hyperthyroidism
- Cushing’s Syndrome: Important to ask for Exogenous Steroid use / TCM
- Hyperparathyroidism
- Hypogonadism (eg: Klinefelter’s)
- CKD: Secondary & Tertiary hyperPTH; Low Vitamin D
GI Causes
- Liver Disease: due to low Vitamin D
- Nutritional deficiencies (chronic alcoholism, malabsorptive disorder, IBD, malnutrition, Coeliac disease)
Drug causes
- SSRI, Antiepileptics
- Exogenous Steroid use / TCM
Rheumatological causes eg; Rheumatoid Arthritis
ID cause eg: HIV
Others e.g. Multiple myeloma – causes lytic lesions
What is the history to take in a patient with osteoporosis?
Risk Factors for osteoporosis
- CKD, CLD, Endocrine conditions
- Prolonged steroid use
- FHx of Osteoporosis / Osteoporotic Fractures
- PMHx of fractures
- Early menopause / Surgical Menopause
- Smoking
FRAX (Fracture Risk Assessment Tool)
- advanced age
- previous fracture
- glucocorticoid therapy
- low body weight
- current cigarette smoking
- excess alcohol consumption
- rheumatoid arthritis
- 2’ osteoporosis (e.g. hypogonadism or premature menopause, malabsorption, chronic liver disease, IBD)
What are the investigations required for osteoporosis?
Laboratory
- FBC: any inflammation, chronic illnesses
- Renal Panel, LFTs (including albumin, AST)
- Ca/Mg/Po4: Hormonal patho & CKD can lead to derangements
- 25[OH]D: to pick up Vit-D Deficiency
Imaging
- XR – if # (Visualise trabeculae, identify pathological fractures)
- DEXA for BMD
Why do we need to correct calcium for albumin?
When measuring 🡪 we measure the TOTAL Ca i.e. both Bound and Unbound
When albumin ↓ 🡪 Ca bound to Albumin ↓ but unbound Ca remains unchanged
Since ionised unbound Ca is what exerts effects, pt has falsely low measured ions
Treatment in this case should not be Ca infusion!
Corrected Ca = Measured Ca * 0.02 (40-albumin)
What are additional assessents to evaluate for etiology of osteoporosis?
Serum TSH, fT4: Assess for hyperthyroidism
Serum PTH: Think HyperPTH when HyperCa, Hypercalciuria, Stones, Osteopenia
Serum and Urine Protein Electrophoresis
- Assess for multiple myeloma/cancer; Suspect when hypercalcemia, weight loss, anemia, proteinuria
- CRAB = HyperCa, Renal Impairment, Anaemia, Bony Lesions
24hr Urinary Cortisol / LD-DST / Late night salivary cortisol: Cushing’s Syndrome;
24-hour urine for calcium and creatinine
- Assess adequate Ca intake in GI disease e.g. IBD/Surgery
- Necessary if kidney stones present, to look for idiopathic hypercalciuria (FHH)
Serum Testosterone & SHBG – Assess hypogonadism in men
FSH, LH, E2 – to assess hypogonadism for women
What is the non pharmacological management of osteoporosis?
Calcium
- Requirement is 1200mg daily in postmenopausal; 1000mg daily in premenopausal/men
- If inadequate intake, can take calcium supplements (500 to 1000mg/day but aim to give ≤50% of requirement via pills, ≥50% from diet because Ca pills increases CV risk by causing calcification in vessels
Smoking and Alcohol Cessation
Exercise
- Appropriate exercise 30 minutes 3 times a week
- Effect on BMD is small, but may reduce # via ↓ fall risk/
↑ muscle strength
resistance exercise, weight bearing exercises (e.g. running, weight lifting)
What are the indications of pharmacological therapy in patients with osteoporosis?
Patients with osteoporosis (fragility fracture or T score ≤ -2.5)
High risk patients with osteopenia (T score b/n -1 to -2.5);
However: All pt must have normal Ca and 25-VitD levels prior to starting therapy, and they should receive supplemental elemental calcium and vitamin D
What is the initial therapy to begin in patients with osteoporosis?
Oral Bisphosphonates e.g. Alendronate: Every week
- Inhibits osteoclasts; leading to indirect increase in BMD
- Oral, take on empty stomach, with full glass of water; take first thing in the morning, sit upright for 30min (causes GI irritation if supine)
What are the side effects of oral bisphosphonates?
Hypocalcaemia
GI side effects – Diarrhoea, nausea, GERD (esophagitis)
Osteonecrosis of jaw (<1%, after tooth extraction/ infection usually)
Atypical Femoral Fracture (AFF) – on prolonged IV bisphosphonate use (>3 years)
What is osteonecrosis of the jaw?
Usually occur after dental procedure while on meds!. Hence, we refer dentition to remove these teeth first BEFORE starting meds
Bisphosphonates (and denosumab) prevent bone healing 🡪 causing prolonged exposure of mandible 🡪 increased risk of infection 🡪 osteonecrosis
Hence for patients, we often ask them to get rid of bad teeth before starting on medications that increases risk of ONJ
What are the C/Is to oral bisphosphonates?
CKD: eGFR <35 (mechanism is unknown, but risks causing AKI/ AoCKD)
Oesophageal Disorders e.g. achalasia (can cause oesophagitis)
Bariatric Surgery (can cause anastamotic ulcers)
BGIT
What is the second line therapy of osteoporosis? What is the - MOA - route of administration - indication?
Denosumab (inhibits osteoclasts hence SE are similar to Bisphosphonates)
MoA
- Monoclonal Ab that serves as RANKL Inhibitor
- RANKL is produced by osteoblasts and stimulates osteoclastogenesis by acting on RANK on osteoclasts.
Administration: Subcutaneous injection, every 6 months
Use – Patients that are not adherent to oral bisphosphonates, avoid IV bisphosphonates, impaired renal function 😊
What are the side effects of denosumab?
Similar side effects as bisphosphonates because they are both inhibitors of osteoclasts
- Hypocalcaemia
- Osteonecrosis of jaw (<1%, after tooth extraction /infection usually)
- Infusion related reaction
- Atypical Femoral Fracture (AFF) – on prolonged IV bisphosphonate use (>3 years)
However, Denosumab is given SC 🡪 hence no GI side effects
How do you manage severe osteoporosis (T-score of -3.5 or below even in the absence of fractures or T-score of -2.5 or below plus a fragility fracture)? How is it administered?
Teriparatide (a PTH analogue!): PTH analogue that induce osteoblastic bone formation by daily administration
Non-Continuous, daily SC PTH administration (in the case of Teriparatide)
- Short ½ life of PTH 🡪 causes daily pulsatile fluctuations 🡪 will stimulate osteoblasts instead
- Since it DIRECTLY builds bone – it is the most powerful medication out of all of the above! 🡪 but is V expensive, only given as last resort!
Administration – Subcutaneous injection daily, for maximum duration of 2 years
What are the side effects of Teriparatide (a PTH analogue!)
Hypercalcemia (due to PTH effects), GI side effects
However, cannot be given >2Y 🡪 excessive bone building may cause osteosarcoma (bone CA)
What is the C/I of Teriparatide (a PTH analogue!)?
- HyperCa (will worsen hyperCa)
- Hx of ANY form of CA, treated or untreated (Teriparatide encourages bone mets)
- Pt refused trtmt or BMD
- CKD: eGFR < 30
- Life expectancy <1y due to terminal illness
- Pt is bedbound -> trtmt is for reducing risk of recurrent #s, while bedbound pts have v low risk of #
How do you monitor osteoporososi?
DXA (Spine and Hip): Follow up in 1 to 2 years. Less frequent monitoring thereafter if condition is stable
If decrease in BMD,
- Ascertain compliance and other factors e.g. new medical conditions
- If change in BMD <5%, continue same therapy and repeat BMD 2 years later
- If change in BMD ≥5%, switch to IV bisphosphonates /🡪 Teriparatide/ 🡪 Denosumab
What are the indications for screening of osteoporosis? Screening every 2-5 years
All women >65 years
All men >70YO
Adults who have a fracture after age 50
Postmenopausal women <65YO w/ OSTA > 20
- OSTA = Osteoporosis self-assessment tool for Asians (OSTA)
- OSTA = Age – BW (kg); high risk if >20
Postmenopausal women <65YO w/ OSTA 0-20 w/ other RF:
- Early menopause POI (i.e. <40YO)
- Prolonged steroid use (≥ 5 mg prednisolone/day or equivalent for ≥ 3 months)
- Family history of fragility fracture
