Musculoskeletal System, Nervous System & Bioelectricity: Calcium, Biominerals and Treatment of Osteoporosis

Flashcards covering key concepts from musculoskeletal system, nervous system, and bioelectricity, focusing on calcium, biominerals, bone composition, remodeling, osteoporosis, and treatments.

What are the common forms of calcium in inorganic minerals?

Calcium can be found as CaCO3 (Aragonite or Calcite), CaSO4 (Anhydrite, Gypsum, or Plaster of Paris), and Ca5(PO4)3(X) (Apatite, where X can be OH, F, Cl).

How is calcium found in the bones and teeth of vertebrates?

Calcium is present as hydroxyapatite in bones and teeth of vertebrates.

What percentage of the human body's mass is made up of calcium?

Calcium makes up 1.5% of the human body's mass, with 99% of it found in bones and teeth.

What are the three main functional roles of calcium in the human body?

Calcium has structural roles (in bones and teeth), signalling roles (blood vessel constriction, nerve impulses, muscle contraction, hormone secretion, vision/taste/smell), and acts as a co-factor in proteins and enzymes (e.g., blood clotting).

Where does calcium absorption primarily occur in the human body?

Calcium absorption primarily occurs in the duodenum due to its low pH, as the solubility of calcium salts increases when pH decreases.

Name two factors that enhance calcium absorption.

Calcium absorption is enhanced by Vitamin D (promotes synthesis of calcium binding protein) and lactose (maintains calcium in soluble form).

Name two factors that inhibit calcium absorption.

Calcium absorption is inhibited by oxalic acid and phytic acid (which form insoluble complexes with calcium) and a high-fat diet (due to insoluble calcium salts formed with fatty acids).

What are the two main types of bone structure in the adult skeleton?

The adult skeleton comprises cortical (compact) bone, which is dense and low porosity, and trabecular (cancellous) bone, which is low density and high porosity.

What are the main organic and inorganic components of bone?

Bone is structurally composed of an organic matrix (mainly type 1 collagen and osteocalcin) and inorganic minerals (primarily calcium hydroxyapatite).

What is the molecular formula of hydroxyapatite, the biomineral calcium compound found in bone?

The molecular formula of hydroxyapatite is Ca5(PO4)3(OH).

How does the percentage of mineralisation affect bone properties?

An increase in mineral component increases stiffness and reduces flexibility, while a decrease enhances flexibility and reduces stiffness.

What are the three special types of cells found in bone?

The three special types of cells found in bone are osteoclasts (bone-degrading), osteoblasts (bone-building), and osteocytes (most abundant, sense bone deformation).

What is the primary function of osteoclasts?

Osteoclasts are responsible for bone resorption (bone-degrading).

What is the primary function of osteoblasts?

Osteoblasts are the cells that form new bone, producing osteoid and controlling calcium and mineral deposition.

What is the difference between bone modeling and remodeling?

Modeling involves independent activities of osteoblasts and osteoclasts for skeletal development and shaping, while remodeling involves sequential and coupled activities of osteoclasts and osteoblasts to renew the adult skeleton.

What are the four phases of bone remodeling?

The four phases are Activation (recruitment of osteoclasts), Resorption (bone degradation by osteoclasts), Reversal (apoptosis of osteoclasts and recruitment of osteoblasts), and Formation (osteoblasts deposit and mineralize new bone matrix).

What role do the 400 Å gaps between tropocollagen subunits play in bone formation?

These gaps act as potential nucleation sites for the deposition of hydroxyapatite crystals, the mineral component of bone.

What is osteoporosis?

Osteoporosis is a bone disease characterized by a significant reduction in bone amount, impaired structural integrity of trabecular bone, and more porous and thinner cortical bone, leading to weak bones prone to fracture.

What is a primary cause of age-related bone loss?

Age-related bone loss is caused by increased bone resorption and reduced bone formation, with accelerated bone loss in postmenopausal women due to low estrogen levels.

Name three risk factors for developing osteoporosis.

Risk factors for osteoporosis include female gender, increased age, estrogen deficiency, low weight/BMI, family history, smoking, prior fracture, corticosteroid use, poor diet/malnutrition, and reduced physical activity.

What is the main mechanism of action for most existing osteoporosis therapies?

Most existing osteoporosis therapies are antiresorptive agents that inhibit osteoclast-mediated bone resorption.

Why is Estrogen-Replacement Therapy (ERT) no longer widely recommended for osteoporosis prevention, despite its benefits?

Despite preventing bone loss and fractures, ERT is no longer widely recommended due to adverse effects like increased risk of cardiovascular disorders and increased risks of endometrial and breast carcinoma.

What are Selective Estrogen-Receptor Modulators (SERMs), and how do they work?

SERMs are therapeutic agents (e.g., Raloxifene) that inhibit bone resorption through a similar mechanism as estrogens, reducing bone turnover and preventing bone loss and fractures, without the same adverse effects as estrogen.

How does Calcitonin treat osteoporosis?

Calcitonin, a 32-amino acid peptide, inhibits osteoclasts by binding to calcitonin receptors expressed by mature osteoclasts, leading to an increase in bone mineral density.

What are Bisphosphonates, and why are they a first-line therapy for osteoporosis?

Bisphosphonates are synthetic analogues of inorganic pyrophosphate with degradation-resistant P-C-P bonds. They are first-line therapy because they block bone resorption immediately, bind with high affinity to hydroxyapatite, and reside in bones for long periods, inhibiting resorption even after discontinuation.

How do non-Nitrogen-containing bisphosphonates inhibit osteoclasts?

Non-N-containing bisphosphonates are internalized by osteoclasts, metabolized, and used to form ATP analogues that accumulate in the osteoclasts, inhibiting ATP-dependent functions and leading to osteoclast apoptosis.

How do Nitrogen-containing bisphosphonates (N-BPs) inhibit osteoclasts?

N-BPs inhibit an enzyme required for the biosynthesis of isoprenoid lipids, which are essential for modifying proteins involved in osteoclast signalling. This leads to protein dysfunction and dysregulation of cell processes, ultimately causing osteoclast apoptosis.