Bone Disorders Flashcards
background on bone structure and composition (read only)
99% of the Calcium in our bodies is found in our
bones which serve as a reservoir for Ca2+ storage.
• 10% of total adult bone mass turns over each year
during remodeling process.
• During growth rate of bone formation exceeds
resorption and skeletal mass increases.
• Once adult bone mass is achieved equal rates of
formation and resorption maintain bone mass until
age of about 30 years when rate of resorption begins
to exceed formation and bone mass slowly
decreases.
3 types of bone cells (read only)
Osteoblasts: the differentiated bone forming cells
and secrete bone matrix on which Ca2+ and PO43-
precipitate.
• Osteocytes: the mature bone cells are enclosed in
bone matrix.
• Osteoclasts: a large multinucleated cell derived from
monocytes whose function is to resorb bone.
Inorganic bone is composed of hydroxyapatite and
organic matrix is composed primarily of collagen.
Calcium Metabolism (read only)
Ca is the most abundant mineral in the body.
• Ca salts in bone provide structural integrity of the skeleton.
• The amount of Ca is balanced among intake, storage, and excretion.
• This balance is controlled by transfer of Ca among 3 organs: intestine, bone, kidneys.
• Ca ions in extracellular and cellular fluids are essential to normal function of a host of biochemical processes
Turnover of Bone Minerals
read only
About 1000 mg of Ca is ingested per day.
• About 200 mg of this is absorbed into the body.
• Absorption occurs in the small intestine, and requires
vitamin D.
• The major site of Ca excretion in the body is the
kidneys.
• The rate of Ca loss and reabsorption at the kidney
can be regulated.
• Regulation of absorption, storage, and excretion of
Ca results in maintenance of calcium homeostasis.
• The plasma Ca concentration is regulated by PTH,
Vitamin D and calcitonin.
Phosphate Metabolism (read only)
P is an essential mineral necessary for ATP, cAMP
2nd messenger systems, and other roles.
• Phosphate absorption is an energy-requiring process
regulated by calcitriol.
• Phosphate deposition in bone, as hydroxyapatite,
depends on the plasma concentration of PTH, which,
with calcitriol, mobilizes both Ca2+ and phosphate
from the bone matrix.
• Phosphate is excreted by the kidney; here PTH
inhibits reabsorption and thus increases excretion
Osteoporosis
what is it?
The total bone mass of humans peaks at 25-35 years
of age.
• Men have more bone mass than women.
• A gradual decline occurs in both genders with aging,
but women undergo an accelerated loss of bone due
to increased resorption during menopause.
• Bone resorption exceeds formation.
• Reduced bone density and mass: osteoporosis
• Susceptibility to fracture.
• Earlier in life for women than men but eventually both
genders are affected
what are 2 types of agents that can treat osteoporosis?
- antiresorptive drugs
2. anabolic agents
how do antiresorptive drugs work?
decrease bone loss, e.g. bisphosphonates, calcitonin, selective estrogen receptor modulators (SERMs), denusomab , calcium
how do anabolic agents work?
which has both actions of antiresorptive and anabolic?
that increase bone formation, e.g. PTH, teriparatide .
•Strontium has both actions (antiresorptive and anabolic).
what can treat rickets and osteomalacia?
what can treat Paget’s disease
•Rickets and osteomalacia are treated with vitamin D
preparations.
•Paget’s disease is treated by bisphosphonates such as
pamidronate or zoledronate and calcitonin
Bisphosphonates (BPs)
name 2 types and common drugs of each
Aminobisphosphonates: (2 phosphates and an amino group)
alendronate, risedronate, pamidronate, zoledronate
Non-Aminobisphosphonates: etidronate,clodronate
Bisphosphonates (BPs)
main action?
what reduces their absorption
where are they eliminated?
Bisphosphonates (BPs) inhibit osteoclast activity through a variety of mechanisms.
- inhibit bone resorption
• BPs have very low oral bioavailability (~1%), and their
absorption is further reduced by food and by divalent
cations such as calcium. recommended that BPs be taken on an empty stomach, with plain
water.
• The BPs that are absorbed are highly bound to bone,
and are not metabolized. They are eliminated by the
kidney.
• The oral BPs are typically administered once weekly
Bisphosphonates (BPs)
how do aminobisphosphonates work?
Disrupt the mevalonate pathway, a pathway involved in the posttranslational modification of proteins that are involved in cellular signaling.
Disruption of the mevalonate pathway interrupts
osteoclast function and leads to apoptosis of the osteoclast
Bisphosphonates (BPs)
how do non-aminobisphosphonates work?
Increase the accumulation of cytotoxic metabolites within osteoclasts, interfering with their function and possibly leading to osteoclast cell death
Bisphosphonates (BPs)
Indications (8)
• Osteoporosis
• Paget’s disease of the bone (results in enlarged, deformed bones) - enlarged soft bone w/ less calcium
• Hypercalcemia:
• Malignancy
• Primary hyperparathyroidism (continuous parathyroid
hormone [PTH] release causes bone demineralization)
• Bone metastasis causing osteolysis:
• Multiple myeloma
• Bone metastases of malignant tumors
Bisphosphonates (BPs)
contraindications (2)
Hypocalcemia (low calc): BPs have exhibited decreases in serum calcium. It is recommended that deficiencies in calcium be addressed before initiation of therapy.
Poor renal function: BPs are eliminated renally
