Metabolic bone diseases Flashcards
1
Q
Osteoporosis
A
- Systemic skeletal d/o characterized by: low bone mass, micro architecture deterioration, increased susceptibility to fracture
- Normally bone breakdown and bone formation are coupled and equal
- In osteoporosis there is an uncoupling of this process and a net loss in bone mass
- This means increased breakdown, decreased formation, or both
2
Q
Pathophysiology of primary osteoporosis 1
A
- Most common cause is bone breakdown exceeding bone formation
- Usually this is due to sex steroid deficiency (estrogen) in post menopausal women
- Asian and caucasian women are the ones most at risk
- Old age is major risk factor (lose 1% of bone mass every year after age 35)
- Other risk factors: family Hx (genetic components), lack of weight bearing exercise, prior Hx of fracture, low Ca diet, etoh/tobacco use, small body size, nulliparity
3
Q
Pathophysiology of primary osteoporosis 2
A
- Estrogen deficiency leads to increased RANKL and cytokine (IL1, IL6) release, along w/ decreased OPG
- This means post menopausal women are in a chronic bone resorption state and are the most at risk for osteoporosis
- Areas most at risk: hip, spine, wrist
4
Q
Secondary causes of osteoporosis 1
A
- Failure to develop normal bone mass: poor development, malnutrition, lack of exercise
- Endocrine deficiency or excess: hypogonadism, cushing’s syndrome (GCCs inhibit blast activity), hyperthyroidism (high T3 causes increased clast and decreased blast activity), hyperpara (high PTH levels will cause the blasts to activate clast and leading to overall increased breakdown)
- TZDs (Glitazones): decrease blast number (divert them to fibroblasts) and increase cytokines leading to increased breakdown
5
Q
Secondary causes of osteoporosis 2
A
- MM: IL1 increases clast activity, MP6 inhibits blast activity
- Organ Tx: chronic illness leads to hypogonadism + GCC use + anti-rejection (immunosupp) drugs lead to Mg def
- Mg def: increases cytokines in bone (increases clast activity), can be due to drugs, bariatric surgery/malabsorption
- Rheumatologic diseases (chronic disease) increased cytokines and clast activity
6
Q
Clinical features of osteoporosis
A
- Thoracic and lumbar vertebra most common fractures (2/3rds are ASx)
- Predicts future spine/hip fractures
- Femur are most serious fractures
- Acute pain on lifting or chronic persistent back pain (many spine fractures are insidious)
- Loss of height/kyphosis
- Disability and depression
7
Q
Assessment of osteoporosis: radiology
A
- Spine Xray most useful: look for ballooning of nucleus puposi (fish mouthing) into vertebral bodies and compression fractures (anterior wedge)
- Look for osteopenia (radiolucent bone)
- 30-50% of bone must be lost to be seen on Xray
- Xrays CANNOT distinguish osteoporosis from osteomalacia
8
Q
Assessment of osteoporosis: bone mineral density (BMD) and labs
A
- Dual energy X-ray is gold standard
- Looks at vertebra, proximal femur, total body Ca
- Will give 2 scores: T and Z score
- Z score only useful in pediatrics
- T score <-2.5 of any bone means the pt has osteoporosis
- T score btwn -1 and -2.5 is osteopenia (above -1 is nl)
- Every drop by 1 unit and risk of fracture increases 2-3x
- Also want to look at labs: 1,25OHD levels, TSH, Ca/PTH, alk phos (alk phos is marker for bone turnover)
- Ca, PO4, alk phos are usually nl except hyperthyroidism (all elevated) and hyperpara (all elevated but PO4, which is reduced)
- In nutritional osteomalacia alk phos is elevated (to maintain Ca levels), 1,25OHD is decreased, and possibly hypoCa (if severe)
9
Q
Non-pharmacological approach to preventing osteoporosis
A
- Adequate Ca intake (1500mg of Ca total each day)
- Adequate 1,25OHD intake (2000units each day)
- Regular load-bearing and strength-training exercise
- Fall prevention programs
10
Q
Rx of osteoporosis 1
A
- Sex steroid replacement Rx: estrogen replacement has been shown to increase bone density in post-menopausal women
- Estrogen replacement (HRT) must be initiated early on after (or just before) menopause
- Starting HRT too long after menopause increases risk of CAD and breast CA
- HRT reduces RANKL/cytokine production and increases OPG production, this decreases risk of fractures
- Calcitonin: stabilizes BMD and will decrease risk of spine fractures by inhibiting osteoclasts
- Selective estrogen receptor modulators (SERM): same as calcitonin it reduces risk of spine fractures but not hip
11
Q
Rx of osteoporosis 2
A
-SERMs will activate the bone estrogen receptor and antagonize the uterus and breast estrogen receptor
-Ex of SERM: raloxifene
-Bisphosphonates (BPPs): prevent osteoclasts from binding to bone and inhibit osteoclast formation of acid (used to breakdown bone)
-BPPs decrease bone loss (increase BMD) and decrease fracture rate
-Ex: zoledronic acid (ZA), alendronate (all of the “dronates”)
PTH: short (<24hrs) doses of PTH activate the osteoblasts more selectively and thus increase bone formation
12
Q
Side effects of bisphosphonates
A
- Oral: upper GI distress (1/3rd), flu-like Sx, osteonecrosis of jaw (very rare, increased frequency in CA pts)
- No increase in Afib
- Can lead to frozen bone (inhibited osteoclasts can’t repair micro fractures), thus consider drug holidays
- IV ZA side effects: severe flu-like syndrome, nephrotoxic (cannot use in renal failure), no increase in Afib, no osteonecrosis of jaw
13
Q
Guidelines for BMD screening
A
- All women 65 and older
- Postmenopausal women w/ 1+ risk factors (other than menopause)
- All post menopausal women w/ fragility fracture
- No recommendations for men
14
Q
Goals for Rx
A
- Fracture reduction
- Stabilize or increase bone mass (magnitude of BMD change does not correlate w/ fracture reduction)
- Must have tolerability and long term safety
15
Q
Guidelines for osteoporosis Rx
A
- All women w/ T score ≤-2.5
- All women w/ T score ≤-1.5 w/ risk factor other than menopause (osteopenia on its own is not enough for Rx, must have risk factor)
- All post menopausal women who have had a fragility fracture
