osteoporosis osteomalacia pagets Flashcards
synthesized by osetoblasts, key regulator of phosphate homeostasis
FGF23
osteoclasts secrete ___ to disolve ____ and ____ to degrade bone matrix proteins
secrete HCl to dissolve mineral and cathepsin K to degrade bone matrix proteins
oral bisphosphponates
side effects + contraindications
aalendronate
risedronate
esophogeal irritation
contraindicated for pt with GFR
osteomalacia =
undermineralized bone matrix leads to weakened bone architecture
Antiabsorptives
Denosumab
Calcitonin
side effects calcitonin
tachyphylaxis - rapid loss of response to drug
nausea
Anabolic + mechanism
Teriparatide - fragement of parathyroid hormone, PTH stimulates bone remodeling
(continuous admin leads to bone loss)
in adution to promoting phophaturia, FGF23inhibits expression of ____ thereby ___-
it also increases activity of 24-hydroxlyase, increasing ___
inhibits expression of 1-hydroxylase, thereby reducing vitamin D activation
activity of 24-hyrdroxylase increasing vitamin D clearance
pathophys Autosomal dominant hypophopphatemic rickets
X-linked and Autsomal recessive
AD = mitations in argiinate residues preventing normal proteolytic degradation of FGF23
X-linked - PhEX gene mutations prevent normal proteolytic degradation
AR = DMP1 mutations prevent degredation
interfaces between osteons
cement lines
selective estrogen receptor modulators for low BMD
mechanism
tamoxifen
raloxifene
prevent increased remodeling
PTH levels in osteomalacia
underlying mechanism
elevated, mineral diciency drives secondary hyperparathyroidism
pathophys Paget’s disease
presentation
unregulated bone turnover > woven, increased intravascularity
headache
deafness (impingent)
limb bowing
increased risk of osteosarcoma
IV bisphosphonates
side effects and contrandications
pamidronate
zoledronic acid
hypocalcemia,
acute phase rxn (flu-like symptoms)
contrainidicated for pt with GFR
tamoxifen side effects
alternate indications
increased thromboembolic risk
breast cancer adjunct
tumor induced osteomalacia pathophys and presentation
benign tumor of mesenchymal origin secreting large amounts of FGF23
serum phos falls and patients develop fatigue and proximal weakness
osteomalaic with detectable bone lonss on DXA
in osteomalacia, osteoid surface volume is
increased
relative bone volume, cortical vs trabecular
80-90% cortical bone
inhibit converion of mevalonate to farnesyl, interfering with protein moification in osteoclasts, leading to apoptosis
Bisphosphonates
alendronate,
risedronate
panidronate
zoledrinc acid
osteopororsis =
compromised bone strength due to bone densitiy and bone quaility that leads to increased risk of fracture
pathophys of vitamin D resistant rickets
mutations of 1-hyroxylase encoded by CYP27B1 and
Vitamin D receptor encoded by VDR
signs of proper osteoblast activity in osteomalacia
elevated P1NP
elevated Alk Phos
people do not suffer from low bone mineral density unless
fractures
Chronic negative Ca blance leads to _____ and if significantly prolonged, _____
secondary parathyroidism, if sufficiently prolonged, osteomalacia
accounts for 80% of bone turnover
trabecular
Denosumab mechanism
side effects
decoy of receptor for RANK-L > prevents osteoclast differentiation
ONJm atypical femoral fractures
increase risk of skin infection
nauea, weakness, fatigue
___ and ___ are potent activators of osteoclast activity, providing free Ca and PO4
PTH
1,25diOHD
pseudofracture of femur common in ricketts
looser zone fracture
compressive strength comes from
tensile from
compressive from mineral
tensile strength from protein (predominantly type 1 collagen)
