Metabolic Bone Disease Flashcards
If there are increased calcium levels the x gland releases x?
the thyroid gland releases calcitonin
When calcitonin is released what happens?
osteoclast activity is inhibited and calcium reabsorption in the kidneys decreases, so calcium level in the blood decreases
If there is decreased calcium levels the x gland releases x?
parathyroid glands release PTH
When PTH is released what happens?
osteoclasts release calcium from bone, calcium is reabsorbed from urine by the kidneys, calcium absorption in the small intestine via vitamin D synthesis; so calcium level in the blood increases
What is bone remodeling?
orderly process of bone resorption and subsequent bone formation AKA “coupling”
90-95% of bone cells are?
osteocytes
What do osteocytes do?
actively secrete and calcifies bone matrix material; regulate bone resorption and formation
Osteocyte activity produces
active release of cytokines needed for osteoclast development
What receptors and inhibitors regulate and control osteoclast production?
RANKL and OPG
What is bone mineral density?
amount of bone acquired during adolescence and young adulthood
Factors impacting the remodeling process
hormones, physical activity, nutrition, genetic influence
When is peak bone mass of the proximal femur?
18-20
When is peak bone mass of the spine?
25-30
What is osteoporosis?
skeletal disorder defined by decreased bone strength and increased fracture risk
What’s the most common metabolic bone disease?
osteoporosis
What fractures are associated with osteoporosis?
fragility fractures
Primary causes of bone loss
aging, estrogen status (age of menopause), nutrition (Ca/vitamin D), peak bone mass, genetics, level of physical activity
Who is more affected by osteoporosis?
women
What’s considered juvenile osteoporosis?
8-14 y/o
Stage I osteoporosis impacts?
post-menopausal women (ages 51-75)
Stage I osteoporosis is?
accelerated trabecular bone loss
Common fractures with stage I osteoporosis?
vertebral body and distal forearm fractures
Stage II osteoporosis impacts?
men and women aged >70
Stage II osteoporosis is?
both trabecular and cortical bone loss
Common fractures with stage II osteoporosis?
wrist, vertebra, hip
Secondary osteoporosis impacts who more?
men
What’s secondary osteoporosis?
underlying factor has been identified like environmental factor or disease state
Environmental factors of osteoporosis?
poor nutrition, calcium/vitamin D deficiency, physical inactivity, decreased sun exposure, medications, tobacco use, alcohol use (>3 drinks/day), traumatic injury (NWB/bed ridden), high caffeine intake
Medications associated with osteporosis
PPI, chronic corticosteroid use >3 months, aromatase inhibitors, anticonvulsants, anticoagulants, SSRI, excessive thyroxine, chemotherapy
Secondary causes of bone loss
hypogonadism, Cushing’s, hyperparathyroidism, hyperthyroidism, DM, hyperprolactinemia, vitamin D deficiency, alcohol, malabsorption, chronic liver disease, primary biliary cirrhosis, gastrectomy, multiple myeloma, OI, Marfan, RA, immobilization
Osteoporosis is most common at age?
> 70
Osteoporosis is common at what age in post-menopausal women?
50-70
Wrist fractures due to osteoporosis are common at what age?
50-59
Vertebral fractures due to osteoporosis are common at what age?
seventh decade
Hip fractures due to osteoporosis are common at what age?
50+; most common in eighth decade
Non-modifiable osteoporosis risk factors
personal history of fracture as adult; history of fracture in primary relative, white race, advance age (>50), female, dementia, poor health, amenorrhea
Modifiable risk factors for osteoporosis
current cigarette smoking, low body weight (<127 lbs/BMI), estrogen deficiency, low lifetime calcium intake, alcoholism, recurrent falls, inadequate physical activity, poor health
Osteoporosis symptoms
silent with no signs or symptoms
Major osteoporotic fracture sites
spine T11-L2 (don’t even have to fall), proximal femur, distal forearm, proximal humerus
Careful evaluation of what for osteoporosis?
measure height loss (>4 cm since young adult maximum height suggest prior vertebral fractures or scoliosis); BMI; Kyphosis; spinal TTP and percussion
FRAX takes into account what?
demographics, previous fracture, parent fractured hip, current smoking status, glucocorticoids, RA, secondary osteoporosis, alcohol (>3 units/day), femoral neck BMD from DEXA
Osteoporosis work up labs
serum BMP (evaluate renal/hepatic function), parathyroid levels, CBC (nutritional status and myeloma), thyroid function tests, 25-hydroxyvitamin D-25(OH)D, serum calcium levels, consider 24 hour urine calcium, testosterone levels in men
What are all the labs for osteoporosis really looking at?
secondary causes of bone loss
What do we look for in a 24 hour urine for osteoporosis?
calcium (excess skeletal loss, vitamin D deficiency, malabsorption), creatinine, sodium, and free cortisol (Cushings)
What are the biochemical markers of bone remodeling?
bone-specific alkaline phosphatase (BSAP) and Osteocalcin (OC) in serum; N-Telopeptide cross-links (NTX) and C-telopeptides (CTX) in urine
What do we think of biochemical markers of bone remodeling?
controversial
Imaging for osteoporosis?
x-ray symptomatic area; DEXA to measure BMD
What’s the gold standard for screening and monitoring changes for osteoporosis?
DEXA
What sites should you evaluate with DEXA?
hip, spine, wrist
Dexa T-score
value compared to that of control subjects at peak BMD
Dexa z-scores
value compared to that of patient matched for age and sex
DEXA indications
women 65 years and older and men 70 years and older; younger postmenopausal women; women in menopausal transition with clinical RF for fracture; men 50-69 y/o clinical RF for fracture; adults with conditions or medications associated with secondary osteoporosis
A T-score within x SD of healthy young adult is normal bone density.
1
A T-score between x and x means a low bone density or osteopenia.
-1.0 and -2.5 SD
A T-score of x is a diagnosis of osteoporosis.
-2.5 SD or below
T-score of x + a fragility fracture Severe (established osteoporosis)
-2.5 SD or below + a fragility fracture
The lower a person’s T-score, the lower
the bone density:
A Z-score above x is normal
-2.0
NOF does not recommend routine bone density testing in these age groups.
children, teens, women still having periods and younger men, premenopausal women with no RF, men <70 without RF; women <65 w/o RF
DEXA limitations
doesn’t distinguish between low bone density vs. undermineralized bone matrix (osteomalacia); BMD varies between regions (spinal vs. distal radius)
Repeat testing for women with normal BD or mild osteopenia
up to 10-15 years
Repeat testing for women with moderate osteopenia
3-5 years
Repeat testing for women with advanced osteopenia
usually annually
Repeat testing for women undergoing treatment for osteoporosis
annual BMD
People larger than x pounds DEXA reads may not be as accurate
300 pounds
What can be done to analyze bone density in those larger than 300 lbs
peripheral bone density test at wrist (radius) and heel
Bone density screenings other than DEXA
QCT (quantitative CT of spine), pQCT (wrist and tibia), finger DXA, ultrasound of calcaneus or wrist
First line treatment of osteoporosis
supplemental calcium; women 19-50 and men 19-70 = 1000 mg; women >50 and men >70 = 1200 mg…. supplemental vitamin D: anyone 18-70 = 600 IU/Day, anyone >71 = 800 IU
Which gender is more likely to die within a year after breaking a hip
men
Why are men less likely to experience osteoporosis?
Androgens do not wane abruptly, like menopause; Slow decline in testosterone and estrogen levels
Men’s risk of fracture increases after
70
Osteoporosis risk factors in men
Age >70, low BMI (<20-25), weight loss >10% body weight, physical inactivity, androgen deprivation therapy (treatment of prostate CA), previous fragility fracture, spinal cord injury
What’s osteomalacia?
softening of the bone; decreased mineralization between calcified bone and osteoid
What’s Rickets?
Defective mineralization of cartilage in the epiphyseal growth plates in children
Etiology of osteomalacia?
vitamin D deficiency…hypophosphatemia….Low Vit D/calcitriol levels= decreased Ca+ absorption= hyperparathyroidism= increased urinary phosphate excretion/wasting; chronic renal or liver disease; mineralization inhibitors (aluminum, fluoride)
RF for osteomalacia
living in cold climates (little sun exposure); insufficient dietary ca and vitamin D; malabsorption disorders; hereditary vitamin d deficiency
CM of osteomalacia
asymptomatic, bone pain/tenderness, deformity, muscle weakness, fracture, antalgic gait/difficulty ambulating, muscle spasms, numbness/tingling, + chvostek’s sign
what sign is associated with osteomalacia?
Chvostek’s sign: tap on facial nerve, see twitching of facial muscles, hyperexcitability
Work up for osteomalacia?
CMP, LFTs, phosphate, calcium, alkaline phosphatase, PTH (start to rise with 25(OH)D ais around 31 ng/ml); 25-hydroxyvitamin D (<30 = insufficient; <15-20 = deficient), 1,25 dihydroxyvitamin D
Imaging for osteomalacia?
x-ray, bone biopsy (maybe)
Osteomalacia treatment
Vitamin D replacement
Target vitamin D serum in osteomalacia
> 30 ng/ml
age 0-1 osteomalacia treatment
Initial: 2000 IU q day vs 50,000 IU q week x 6 weeks
Maintenance: 400-1000 IU q day
1-18 osteomalacia treatment
Initial: 2000 IU q day vs 50,000 IU q week x 6 weeks
Maintenance: 600-1000 IU q day
> 18 osteomalacia treatment
initial: 6,000 IU q day vs 50,000 IU q week x 8 weeks
Maintenance: 1500-2000 IU q day
what if a person is getting osteomalacia treatment and has malabsorption?
2-3 x higher dose
What’s paget disease?
Localized bone remodeling disorder; Excessive resorption, then increased bone formation; Disorganized bony structure- weaker and more susceptible to fracture
Etiology of Paget Disease
genetic predisposition; maybe viral, autoimmune, connective tissue disorder, vascular disorder
phases of paget disease
1) lytic phase: osteoclast activity-resorption; increase in number, size, and number of nuclei 2) mixed phase–osteoclast and osteoblast activity; bone resorption and formation leading to disorganized bone formation 3) sclerotic phase–disorganized bone formation becomes vascular, fibrous connective tissue
Paget affects which bones?
PELVIS, lumbar spine, thoracic spine, femur, sacrum, skull, tibia, humerus
Who is more affected by Paget men or women?
men
CM of Paget disease
asymptomatic, bone pain is location specific, if skull (hearing loss, HA, tinnitus, increased hat size, cranial nerve palsies), pathologic fractures
PE of Paget disease
deformities (bowing, kyphosis), decreased ROM, localized TTP, conductive vs. sensorineural hearing loss, abnormal gait
Complications of paget disease
fractures, neoplasms (rare, but osteosacroma from fibrotic tissue), spinal cord compression, cerebellar compression, cranial nerve palsies, degenerative joint disease, left ventricular hypertrophy, calcific aortic stenosis
Imaging of paget
plain films, possibly bone scan
Labs for paget
alkaline phosphatase (bone specific), [calcium, vitamin D, phosphate] = normal, urinary markers (hydroxyproline, deoxypyridinoline, c-telopeptide
Treatment of paget
Bisphosponates ->
Zoledronate acid (Reclast) 5 mg IV
Alendronate (Fosamax) 40 mg x 6 months
Risedronate (Actonel) 30 mg q daily x 2 months
