Bone Metabolism Flashcards
Of the bone matrix, what two things does the organic component consist of?
Type 1 Collagen
Non-collagenous proteins i.e. Osteonectin, Osteopontin, Osteocalcin
Of the bone matrix, what does the inorganic component consist of?
Calcium hydroxyapatite
What is Trabeculae also known as?
Spongy bone, or cancellous bone
How is Trabeculae very light yet has a large surface area?
The bone marrow has been removed from the bone, leaving pores and “bite marks” which increases the surface area
What are the two types of cells involved in bone resorption and deposition?
Osteoclasts and Osteoblasts
What is the function of Osteoclasts?
Bone resorption (bone removal)
What is the function of Osteoblasts?
Bone deposition (bone laying down)
Describe what is meant by the phrase “use it or lose it” in the context of bones
Bones are use-dependent and will reduce in mass in zero gravity / no exercise. 1% of bone mass is lost every month in zero gravity, whereas weight bearing exercises will not only increase muscles but also bones
How much calcium is found within the human body?
1,000 g
What is the normal serum concentration of calcium?
2.25 - 2.6 mmol/L
Ionised calcium is serum is rigidly maintained by what?
Parathyroid hormone (PTH), Vitamin D, Calcitonin
What does coupled bone remodelling refer to?
Bone deposition = Bone resorption
The components of bone matrix are % organic / % inorganic?
40% organic
60% inorganic
Describe the cellular structure of OsteoCLASTS
Large and multinucleated, with up to 40 - 100 nuclei. The more nuclei, the more aggressive they resorb
Describe the cellular structure of OsteoBLASTS
Mononuclei, stromal, non-haematopoetic and mesenchymal
Describe what the role of Osteoblasts are in some detail
Osteoblasts produce Type 1 Collagen which will eventually mineralise into bone matrix
The osteoblasts bury themselves alive in bone matrix as osteocytes, and make connections with other osteocytes via cell extensions
Describe what the role of Osteoclasts are in some detail
Osteoclasts sit on the bone surface and form limpet-like adhesions via integrins. They secrete enzymes and acids to degrade bone matrix forming lacunae
What is the recommended daily intake of Calcium?
1,000 mg
Protein-bound calcium (40% of serum Ca) is bound to…?
Albumin
Complexed calcium (10% of serum Ca) is complexed to…?
Citrate and Phosphate
How much Phosphorus is located in the body?
600 g
What is the normal range for Phosphate levels?
0.9 - 1.3 mmol/L
What are the Phosphate levels in serum primarily regulated by…?
Parathyroid hormone
What is Vitamin D3 also known as?
Cholecalciferol
Cholecalciferol can be ingested in the diet, but also synthesised de novo. How?
Synthesised in the skin from 7-dehydrocholesterol using UV light
How is Cholecalciferol converted to 25(OH) Vitamin D3 (inactive)
Via 25-hydroxylation in the liver
How does 25(OH) Vitamin D3 (inactive) become 1,25 (OH) Vitamn D3 (active)
Via 1-hydroxylation in the kidneys
The synthesis of 1,25(OH) Vitamin D3 is tightly regulated… How?
Synthesis is regulated by PTH
Inhibition is regulated by increased Ca+ and P in serum
What is the purpose of 1,25(OH) Vitamin D3?
Increases calcium and phosphate absorption from the intestine and into the blood
Can also induce marrow monocytes to differentiate into osteoclasts to stimulate bone resorption
How does Vitamin D3 become catabolised?
Via 24-hydroxylation
What is Parathyroid Hormone secreted by?
Parathyroid gland
Parathyroid hormone is secreted in response to…?
Low Calcium levels in serum
Describe the effects of high and low PTH on the skeleton
High levels of PTH: Osteoclastic bone resorption, mobilising calcium FROM bone
Low levels of PTH: Osteoblastic bone deposition, mobilising calcium TO bone
How does the PTHRP usually work, systemically or locally? What about pathologically?
Normally: Local effect
Pathologically: Systemically when secreted in excess during malignancy
Calcitonin is released from…? In response to…? What effect does it have…?
Parafollicular cells of the thyroid
In response to increased plasma calcium
Causes reduced bone resorption
What two sex hormones are important in bone metabolism?
Oestrogens
Androgens
What is the incidence of Osteoporosis in men and women over 50?
Women: 1 in 2
Men: 1 in 5
State five treatments for Osteoporsis
Calcium supplementation Hormone Replacement Therapy Bisphosphonates Calcitonin Selective Estrogen Receptor Modulators
