Lecture 6: Bone Physiology Flashcards
What are bones made from
Primarily made of collagen and hydroxyapatite -
Ca10(PO4)6(OH)2
Skeletal function
Structural integrity+strength to body Protect vital organs Blood cell formation Storage of essential minerals particularly “Calcium”, phosphate, magnesium, and sodium. 10%cardiacout-put.
Key players in skeletal system
Calcium & Phosphates
Parathyroid hormone (PTH).
Cholecalciferol and Calcitriol (Vit.D3).
Estrogen and other Sex hormones.
Calcitonin.
Bisphosphonate ( anti resorptive agents)
three different sub-categories of bone cells related to osteoblasts:
1) the osteoblasts
2) bone lining cells, and 3) osteocytes.
Function of osteoblasts and osteocytes and osteoclasts
Osteocytes = mature bone cells
In lacunae
Connected by canaliculi
Osteoblasts synthesize new matrix
Osteogenesis
Osteoclasts dissolve bone matrix
Osteolysis
Role of PTH and Calcitonin in blood ca level regulation
Calcitonin decreases blood calcium levels
PTH increases blood calcium levels
Target organs for Ca homeostasis
Kidney
Bone
GI tract
How does the kidney, GI tract and bone aid in homestasis
PTH causes kidneys to retain ca ions
PTH causes osteoclasts to increased release of calcium ions from bone matrix
PTH and calcitriol causes intestine to increase rate of absorption of calcium.
Define osteogenesis
Production of bone on soft tissue
What can osteogenesis be divided into
1.intramembranous ossification
process by which flat bones like the skull, mandible and clavicle are formed.
2.endochondral ossification
process is different from intramembranous ossification in that it occurs with a cartilage base. Endochondral ossification is responsible for a good deal of formation of the long bones and vertebrae
Bone modeling characteristics
1)Changes in bone structure occur on existing bone structure
and
2) Bone structure alterations occur by independent action of
osteoblasts and osteoclasts.
Define bone remodeling
osteoblasts and osteoblasts do not act independently but are coupled and bone resorption and formation occur at the same spot on a bone surface.
Bone remodeling process
- Quiescence refers to the resting state of the bone surface. This includes all of the bone surfaces.
- Activation is the recruitment of osteoclasts to a bone surface and signal coupling of osteoblasts.
- Resorption is the removal of bone by osteoclasts.
- Reversal is the process by which osteoclasts stop removing bone and osteoblasts fill the defect.
- Formation is the laying down of bone by osteoblasts
Biochemical markers of bone turnover: Resorption
• Pyridinoline (Pyr) • Deoxypyridinoline (dPyr) • Amino terminal telopeptide of type I collagen (NTX) • Carboxyl terminal telopeptide of type I collagen (CTX)
Biochemical markers of bone turnover: Formation
Osteocalcin (OC) • Bone-specific alkaline phosphatase (BAP) • Amino terminal propeptide of type I collagen (PINP) • Carboxyl terminal propeptide of type I collagen (PICP)
How to asses bone formation
Serum immunoassays for osteocalcin.
Alkaline phosphatase – both types
How to assess boen resorption
Immunoassays for the type I collagen pyridinoline crosslink
What causes Osteoporosis
- Lack of estrogen in women or androgen in men
- Lack of exercise to stress the bones.
- Inadequate intake of calcium and phosphorus. •Abnormalities of vitamin D metabolism.
- Loss of muscle mass.
Define Osteoporosis
More bone removal than bone formation
Osteoporosis is defined as a disease in the bone in which the bone mineral density is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in the bone is altered. Osteoporotic bones are more at risk of fracture.
Role of estrogen
Plays an important role in the growth and maturation of bone as well as in the regulation of bone turnover in adult bone.
Regulate cell death (apoptosis).
Accelerates the death of osteoclasts, while prolonging the life of osteoblasts.
Increase intestinal absorption of calcium
Increase reabsorption of calcium from the renal tubule.
What is Osteopenia and difference to osteoporosis
is a condition that begins as you lose bone mass and your bones get weaker. This happens when the inside of your bones become brittle from a loss of calcium.
The difference between osteopenia is midway point of osteoporosis and bone loss is not as severe as
in osteoporosis. (bone density is lower but not severe).
That means someone with osteopenia is more likely to fracture a bone than someone with a normal bone density but is less likely to fracture a bone than someone
with osteoporosis.
Primary vs Secondary Osteoporosis
Primary osteoporosis is bone loss that occurs during the normal human aging process.
Type 1 primary osteoporosis typically occurs
in postmenopausal women. It is caused by increased activity of osteoclasts, related to decreased levels of estrogen in the circulation.
Type 2 primary osteoporosis, affects both men and women. Bone loss is not related to an increased osteoclastic activity, and the cause of bone loss is obscure. This is SENILE osteoporosis (bone loss that results from aging)
Secondary osteoporosis is defined as bone loss that results from specific, well-defined clinical disorders.
What is Rickets
- Skeletal disorder that’s caused by a lack of vitamin D, calcium, or phosphate.
- Calcium is not deposited in bones.
- Bones become soft.
- Bowing of the bones, and other deformities occur.
Define Osteomalacia
- Disease characterised by the softening of the bones caused by impaired bone metabolism.
- Primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium.
Rickets and osteomalacia may be caused by
u A deficiency or abnormal metabolism of vitamin D
A decrease in serum phosphate and calcium
An increase of ALP and PTH
What causes Vit D deficiency?
a dietary lack of the vitamin
insufficient ultraviolet exposure to form endogenous vitamin D
most commonly, malabsorption interfering with the intestinal absorption of fats and fat-soluble vitamin D.
Define Pagets Disease
is a localized, although sometimes multifocal, skeletal disorder of unknown cause and is characterized by abnormal bone remodeling brought about by waves of bone resorption and defective reformation (forms dense bone).
How does loss of muscle mass AND lack of exercise/stress to bones cause osteoporosis?
lack of exercise/stress to bones:
If you are not causing stress or use of bones, then the body does not see a major use for them. Therefore the body will start to degrade the bones due to lack of use. Therefore major resorption, major bone loss and thus osteoporosis.
loss of muscle mass:
muscle atrophy appears to contribute directly to bone loss primarily via increased bone resorption by osteoclasts, although decreases in irisin levels with disuse may also suppress osteogenesis