Flashcards in Metabolic Bone Disease Deck (46):
How is bone formed?
- osteocytes (bone cells) are embedded in an organic matrix of collagen fibers and noncollagenous protein.
- binding of calcium phosphate in the form of hydroxyapatite crystals.
*constantly renewed (resorption and replacement).
What are the 2 types of bone?
1. CORTICAL= mechanical and protective function.
- TRABECULAR= metabolic function.
What is the metabolic function of trabecular bone?
- to reserve ions (especially calcium and phosphate).
What is the macroscopic organization of bone?
- cortex= compact (cortical) bone (80-90% calcified).
- trabecular= cancellous (spongy) makes up the remainder.
Does trabecular (cancellous/spongy) bone remodel more or less than cortical bone?
- more (80%) compared to cortical bone's 20%, except in women after menopause.
What are the biochemical markers of bone formation?
- serum osteocalcin
- serum alk phos
- serum procollagen I extension peptides.
What are the biochemical markers of bone resorption?
- urinary N-telopeptide collagen crosslinks
- urinary deoxypyridinoline
What is the gold standard test for measuring osteoporosis?
- DEXA scan of vertebral spine or femoral neck
What is Osteomalacia?
- inadequate mineralization of bone matrix, due to low calcium-phosphate product (hypocalcemia, hypophosphatemia or both).
What can cause of osteomalacia?
- vitamin D deficiency (most common)
- renal phosphate loss
- failure of intestinal absorption of calcium, phosphate or vitamin D.
What will you see in Osteomalacia (adults)/Rickets (children)?
- bowing of long bones
- widening of the epiphyses
- bone pain, tenderness, and muscle weakness.
What will teeth look like in vitamin-D resistant Rickets?
- hypoplastic teeth
- caries producing pulpitis
If a pt has Rickets due to lack of 1-hydroxylase in the kidney, how do you treat?
- 1, 25-dihydroxy D3
To what type of fracture does osteoporosis lead most often?
- hip fractures
*be aware in post menopausal women.
Does osteoporosis cause more loss of trabecular or cortical bone?
- more trabecular, but also cortical.
What is Osteoporosis?
- reduction in TRABECULAR bone mass, resulting in porous bone with an increased risk for fracture.
What are the 2 major causes of bone loss?
2. estrogen deficiency (don't forget younger women with hysterectomy).
What demographic is most at risk for osteoporosis?
- Caucasian women or Asian.
- short stature, slender build, small bones.
- Family Hx
- smoking hx
- estrogen deficiency
Can certain disease or drugs cause osteoporosis?
- YES (corticosteroids, alcohol, heparin, thyroxine, cyclosporine...)
What is the most common type of metabolic bone disease?
When do you reach your peak bone mass?
- age 30
What does 1 standard deviation below normal indicate on a DEXA scan?
What type of exercise must pts with osteoporosis do?
- WEIGHT BEARING exercise
In what stage of a woman's life can she lose 1/3 of her bone mass?
- within 5 years of menopause
How will pts with an osteoporosis fracture present grossly?
- kyphosis of the thoracic spine
- height loss
- wedge deformity on x-ray
What are the 2 types of osteoporosis?
1. postmenopausal (type 1)
2. senile (type 2)= old or aged
How does the DEXA scan measure bone density?
- abosolute value (g/cm2) for patient
- comparison to sex and age-matched reference values (Z-score).
- comparison to premonopausal mean peak reference values (T-score or young adult Z-score).
** What is the T-score?
- standard deviations above or below the mean of YOUNG ADULTS.
*the T-score is KEY.
** What is the Z-score?
- standard deviations above or below the mean age, gender, and race matched individuals.
**** What are the T-SCORE criteria for assessing disease severity of osteoporosis? (TEST QUESTION)
- normal= greater or equal to -1.0
- osteopenia (low bone mass)= between -1.0 to -2.5
- osteoporosis= less or equal to -2.5
- severe osteoporosis= less than -2.5 with fracture.
** What is the WHO definition of osteoPENIA?
- bone mineral density is 1 to 2.5 standard deviations below peak bone mass.
** What is the WHO definition of osteoPOROSIS?
- 2.5 standard deviations below peak bone mass.
*** What does the new risk assessment of osteoporosis (FRAX) include?
- bone density plus age, previous fracture, family hx of osteoporosis, steroid use, and smoking.
How do we prevent osteoporosis?
- appropriate calcium and vitamin D intake in diet.
- lifestyle= weight bearing exercise
- HRT beginning in perimenopause
- analgesics for pain as needed.
What drugs do we use for osteoporotic fracture prevention?
- HRT (controversial)
- bisphosphonates (alendronate, risedronate)
- reclast (annually)
What are the potential risks of HRT?
- breast cancer?
- DVT and PE
- breast tenderness
- endometrial cancer with intact uterus (if unopposed)
- weight gain
What are some alternatives to HRT for osteoporosis?
- mixed estrogen agonist/antagonist
- SERM (selective estrogen receptor modulators)= tamoxifen (1st gen) or raloxifene (2nd gen).
How do the bisphosphonates work?
- interfere with cell signaling mechanisms to reduce the resorptive actions of mature osteoCLASTS.
What are some risks of bisphosphonates?
- osteonecrosis of the jaw
- atraumatic long bone fractures
- carcinoma of the esophagus
What is Denosumab? (DRUG OF CHOIC)
- monoclonal antibody directed against RANKL in osteoBLASTS, thus PREVENTING activation of osteoCLASTS.
*injection given every 6 months.
What are the side effects of denosumab?
- increased risk of serious infections
- osteonecrosis of the jaw
*** What is associated with PRIMARY hyperparathyroidism?
- MEN 1= 95% hyperplasia + pancreatic and pituitary tumors.
- MEN 2A= 50% hyperplasia + medullary thyroid cancer and pheochromocytoma.
*** What labs will you see with primary hyperparathyroidism?
- high serum calcium and chloride
- high serum PTH and alk phos
- low serum phosphorous and HCO3-
- high urine calcium
- high urine phosphorous
- high urine cAMP
What is most associated with secondary hyperparathyroidism?
- chronic kidney disease, causing increased phosphorous and decreased calcium, worsening hyperparathyroidism.
Is vitamin D3 or D2 better for supplementation?
- D3 at least 800 IU