Pathophys of metabolic bone disorders Flashcards
Define metabolic bone disease
imbalance of bone remodeling
How can bone remodeling be measured?
biochemical markers of bone resorption and formation
What is cathepsin K?
highly expressed in osteoclast, where it is localized in the lysosome and released in bone resoprtion
Wnt pathway activation _____ new bone formation. What inhibits Wnt signaling?
increases. Inhibited by sclerostin
Sclerostin _____ regulates bone formation
negatively
Bone loss can result in ____, a condition of bone fragility, that is a silent disease until it ends up in fracture.
osteoporosis
Define osteoporosis.
a skeletal disorder characterized by compromised bone strength and an increased risk of fracture.
Bone strength reflects the integration of what two main features?
bone density and bone quality
Important risk factors for fracture
Age: major contributor
Gender: woman>men
BMD
BMI
What are lifestyle risk factors for osteoporosis?
alcohol abuse, smoking, immobilization, excessive thinness, high salt intake
What are nutritional risk factors with osteoporosis?
low calcium intake, low vitamin D intake, excess vitamin A intake.
What hormonal abnormalities with osteoporosis?
hyperparathyroidism, low testosterone or androgen insensitivity, low estrogen (menopause), excess cortisol, thyrotoxicoses, T1D, T2D, adrenal insufficiency
What GI disorders are associated with osteoporosis?
celiac disease, gastric bypass, IBD, GI surgery, malabsorption, pancreatic disease, primary biliary cirrhosis.
What genetic factors are associated with osteoporosis?
CF, ehler-danlos, Gaucher’s, glycogen storage, hemochromatosis, homocystinuria, hypophosphatasis, idiopathic hypercalciuria, marfan, menkes steely hair syndrome, OI, porphyria, riley-day syndrome
What heme disorders are associated with osteoporosis?
MM, hemophilia, thalassemia, monoclonal gammopathies, leukemia and lymphoma, SCD, systemic mastocytosis
What rheum and autoimmune disorders are associated with OP?
ankylosing spondylitis, lupus, RA
What CNS disorders are associated with OP?
epilepsy, MS, parkinsons, spinal cord injury, stroke
In a nut shell, what is associated with OP?
everything. including AIDS. and every drug.
What blood tests should be done if you suspect osteoporosis?
PTH, VD, CMP, PO4, Mg, TSH, testosterone, CBC, 24 hour urine calcium
What is the DEXA bone scan Z score?
bone density compared to age, sex, ethinicity matched reference population
What is the DEXA T score?
bone density compared to a young adult reference population
WHO diagnostic classification does not apply to:
premenopausal women, men less than 50 y/o, children
Indications for bone density testing
women 65 and older, men 70 and older regardless of risk factors
Younger postmen. women or men 50-69 with fracture risk factors.
Any adult with fracture after age 50
Adults with a condition or taking meds associated with low bone mass.
What is the role of vertebral fractures in OP diagnosis?
Any low trauma even painless fracture is consistent with a diagnosis of OP even in the absence of bone density diagnosis. Most are asymptomatic when they occur.
Biochemical markers of bone formation
bone specific alkaline phosphatase, osteocalcin, aminoterminal propeptide of type 1 procollagen
markers of bone resoprtion
Serum C-telopeptide
urinary N-telopeptide
What is FRAX
calculation of the 10 year probability of hip fracture and then 10 years prob. of a major OP fracture. Intended for postmen women and men older than 50.
