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6.6
1.
6.6 Bone Remodeling •
About 5–7% of bone mass is recycled each week – Spongy bone replaced ~ every 3-4 years – Compact bone replaced ~ every 10 years • Bone remodeling consists of both bone deposit and bone resorption – Occurs at surfaces of both periosteum and endosteum – Remodeling units: packets of adjacent osteoblasts and osteoclasts coordinate remodeling process © 2016 Pearson Education, Inc.
2.
Bone Deposit • New
bone matrix is deposited by osteoblasts • Osteoid seam: band of unmineralized bone matrix that marks area of new matrix • Calcification front: abrupt transition zone between osteoid seam and older mineralized bone © 2016 Pearson Education, Inc.
3.
Bone Deposit (cont.) •
Trigger for deposit not confirmed but may include: – Mechanical signals – Increased concentrations of calcium and phosphate ions for hydroxyapatite formation – Matrix proteins that bind and concentrate calcium – Appropriate amount of enzyme alkaline phosphatase for mineralization © 2016 Pearson Education, Inc.
4.
Bone Resorption • Resorption
is function of osteoclasts – Dig depressions or grooves as they break down matrix – Secrete lysosomal enzymes and protons (H+) that digest matrix – Acidity converts calcium salts to soluble forms © 2016 Pearson Education, Inc.
5.
Bone Resorption (cont.) •
Osteoclasts also phagocytize demineralized matrix and dead osteocytes – Digested products are transcytosed across cell and released into interstitial fluid and then into blood – Once resorption is complete, osteoclasts undergo apoptosis • Osteoclast activation involves PTH (parathyroid hormone) and immune T cell proteins © 2016 Pearson Education, Inc.
6.
Control of Remodeling •
Remodeling occurs continuously but is regulated by genetic factors and two control loops 1. Hormonal controls • Negative feedback loop that controls blood Ca2+ levels • Calcium functions in many processes, such as nerve transmission, muscle contraction, blood coagulation, gland and nerve secretions, as well as cell division • 99% of 1200–1400 gms of calcium are found in bone • Intestinal absorption of Ca2+ requires vitamin D 2. Response to mechanical stress © 2016 Pearson Education, Inc.
7.
Control of Remodeling 1.
Hormonal controls – Parathyroid hormone (PTH): produced by parathyroid glands in response to low blood calcium levels • Stimulates osteoclasts to resorb bone • Calcium is released into blood, raising levels • PTH secretion stops when homeostatic calcium levels are reached – Calcitonin: produced by parafollicular cells of thyroid gland in response to high levels of blood calcium levels • Effects are negligible, but at high pharmacological doses it can lower blood calcium levels temporarily © 2016 Pearson Education, Inc.
8.
Figure 6.12 Parathyroid
hormone (PTH) control of blood calcium levels. © 2016 Pearson Education, Inc. Calcium homeostasis of blood: 9–11 mg/100 ml BALANCE BALANCE Stimulus Falling blood Ca2 levels Thyroid gland Osteoclasts degrade bone matrix and release Ca2 into blood. Parathyroid glands Parathyroid glands release parathyroid hormone (PTH). PTH
9.
Clinical – Homeostatic
Imbalance 6.1 • Even minute changes in blood calcium levels can cause severe neuromuscular problems – Hypocalcemia: low levels of calcium cause hyperexcitablility – Hypercalcemia: high levels of calcium cause nonresponsiveness – Sustained high blood calcium levels can lead to deposits of calcium salts in blood vessels or kidneys and formation of kidney stones © 2016 Pearson Education, Inc.
10.
Control of Remodeling
(cont.) 1. Hormonal controls (cont.) – Other hormones play a role in bone density and turnover • Leptin – Hormone released by adipose tissue – May play role in bone density regulation by inhibiting osteoblasts • Serotonin – Neurotransmitter regulates mood and sleep; also interferes with osteoblast activity – Most serotonin made in gut – Secreted into blood after a meal – May inhibit bone turnover after a meal, so bone calcium is locked in when new calcium is flooding into bloodstream © 2016 Pearson Education, Inc.
11.
Control of Remodeling
(cont.) 2. Response to mechanical stress – Bones reflect stresses they encounter • Bones are stressed when weight bears on them or muscles pull on them – Wolf’s law states that bones grow or remodel in response to demands placed on them • Stress is usually off center, so bones tend to bend • Bending compresses one side, stretches other side – Diaphysis is thickest where bending stresses are greatest – Bone can be hollow because compression and tension cancel each other out in center of bone © 2016 Pearson Education, Inc.
12.
Load here (body weight) Head
of femur Compression here Tension here Point of no stress Figure 6.13 Bone anatomy and bending stress. © 2016 Pearson Education, Inc.
13.
Control of Remodeling
(cont.) – Wolf’s law also explains: • Handedness (right- or left-handed) results in thicker and stronger bone of the corresponding upper limb • Curved bones are thickest where most likely to buckle • Trabeculae form trusses along lines of stress • Large, bony projections occur where heavy, active muscles attach – Weight lifters have enormous thickenings at muscle attachment sites of most used muscles • Bones of fetus and bedridden people are featureless because of lack of stress on bones © 2016 Pearson Education, Inc.
14.
Control of Remodeling
(cont.) • Mechanical stress causes remodeling by producing electrical signals when bone is deformed – Compressed and stretched regions are oppositely charged – Compression/tension changes fluid flows within canaliculi, which may also stimulate remodeling • Hormonal controls determine whether and when remodeling occurs in response to changing blood calcium levels, but mechanical stress determines where it occurs © 2016 Pearson Education, Inc.
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