Calcium College of Dentistry Dr Mouaadh Abdelkarim

Learning objectives Describe factors effecting calcium homeostasis Describe the metabolism of Vitamin D and the functions of PTH, and calcitonin Interpret the biochemical changes associated with some metabolic bone disorders

Introduction - fifth most important element in the human body g present in adult - calcium is an essential element that is only available to the body through dietary sources Current dietary calcium recommendations range from mg/d, depending on age.

- in some individuals, particularly the elderly, calcium supplements may be needed to achieve the recommended dietary calcium intake. - calcium metabolism is regulated by three mechanisms: intestinal absorption, renal re- absorption, and bone turnover. - Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis.

Calcium Distribution Calcium plays a key role in a wide range of biologic functions, either in the form of its free ion or bound complexes. One of the most important functions as bound calcium is in skeletal mineralization. The vast majority of total body calcium (>99%) is present in the skeleton as calcium-phosphate complexes

In bone, calcium serves two main purposes: it provides skeletal strength and, concurrently, provides a dynamic store to maintain the intra- and extracellular calcium pools. Nonbone calcium represents <1% of total body calcium ( ∼ 10 g in an adult). However, it is in constant and rapid exchange within the various calcium pools and is responsible for a wide range of essential functions, including extra- and intracellular signaling, nerve impulse transmission, blood coagulation, second mesenger and muscle contraction

Serum calcium ranges from ∼ 8.8 to 10.4 mg/dl (2.2 to 2.6 mM) in healthy subjects. It comprises free ions ( ∼ 51%), protein-bound complexes ( ∼ 40%), and ionic complexes ( ∼ 9%) the concentration of serum ionized calcium is tightly maintained within a physiologic range of 4.4 to 5.4 mg/dl (1.10 to 1.35 mM). Nonionized calcium is bound to a variety of proteins and anions in both the extra- and intracellular pools. The main calcium-binding proteins include albumin and globulin in serum and calmodulin and other calcium- binding proteins in the cell.

Calcium Balance Calcium balance refers to the state of the body stores of calcium at equilibrium over some extended time period (usually days, weeks, or months). Bone balance changes throughout the normal lifespan, depending on relative rates of bone formation and resorption. Children are in positive bone balance (formation > resorption), which ensures healthy skeletal growth.

Healthy young adults are in neutral bone balance (formation = resorption) and have achieved peak bone mass. Elderly individuals are typically in negative bone balance (formation < resorption), which leads to age-related bone loss. Factors that promote positive bone balance in adults include exercise, anabolic and anti- resorptive drugs, and conditions that promote bone formation over bone resorption (e.g., “hungry bone” syndrome, osteoblastic prostate cancer). (antiresorptive medications that slow bone loss and anabolic drugs that increase the rate of bone) Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels

There are three types of bone cells: Osteocytes, the mature bone cells are enclosed in bone matrix. Osteoblasts are the differentiated bone forming cells and secrete bone matrix on which Ca ++ and PO 4 precipitate or deposit. Osteoclasts is a large multinucleated cell derived from monocytes whose function is to resorb bone. Bone cell types

Calcium is taken in the diet as phosphates, carbonates or tartarates. Absorption occurs by active transport.

Synthesis of Vit - D U.V. light on precursors in skin Vit D 25-HCC (Liver) 1,25-DHCC 24,25-DHCC (Kidney) (Kidney)

Actions of Vit-D on Intestines

Actions of Vit-D on bones

Actions of Vit-D on Kidneys

Parathyroid hormone is the most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid. This hormone is secreted from cells of the parathyroid glands and finds its major target cells in bone and kidney. PTH: Mobilization of calcium from bone, Enhancing absorption of calcium from the small intestine, Suppression of calcium loss in urine

Parathyroid Hormone Secreted by parathyroid glands – Rapid response to reduced calcium (minutes) Polypeptide – 84 amino acid residues – 9,500 daltons M.W. Peptide fragments can be active for periods measured in hours Operates in tissues via cAMP second messenger

Action of PTH on bone PTH causes resorption of bone. (osteoclastic activity). This causes mobilization of Ca ++ from the bone or demineralization. Hence it increases serum Ca ++ levels.

Action of PTH on Kidney

Action of PTH on intestine Indirectly By promoting synthesis of calcitirol

Active Control of Calcium Vitamin D3 – Diet and sun Parathyroid hormone – Parathyroid gland Calcitonin – Thyroid gland Skeletal loading – Osteoblasts and osteoclasts

Excessive secretion of parathyroid hormone is seen in two forms: Primary hyperparathyroidism is the result of parathyroid gland disease, most commonly due to a parathyroid tumor (adenoma) which secretes the hormone without proper regulation. Common manifestations of this disorder are chronic elevations of blood calcium concentration (hypercalcemia), kidney stones and decalcification of bone (>>2.63 mmol/l (105 mg/l), free calcium >>1.40 mmol ). Secondary hyperparathyroidism is the situation where disease outside of the parathyroid gland leads to excessive secretion of parathyroid hormone. A common cause of this disorder is kidney disease - if the kidneys are unable to reabsorb calcium, blood calcium levels will fall, stimulating continual secretion of parathyroid hormone to maintain normal calcium levels in blood. Secondary hyperparathyroidism can also result from inadequate nutrition - for example, diets that are deficient in calcium or vitamin D, or which contain excessive phosphorus (e.g. all meat diets for carnivores). A prominent effect of secondary hyperparathyroidism is decalcification of bone, leading to pathologic fractures or "rubber bones".

physiopathology Hypertension (HTA) heart rhythm disorder

CALCITONIN Secreted by the Para-Follicular (C) cells of the Thyroid gland. It is functionally antagonistic to PTH.

Action of CALCITONIN on bone & Kidney

Vitamin D deficiency

Hypoparathyroidism (Tetany) Causes Hypocalcemia,↑ serum phosphate presenting as neuromuscular irritability, numbness, cramps, anxiety, Tetany, carpopedal spasms. Severe Hypocalcemia is followed by convulsions, strider and dystonia. A prolonged QT interval on the ECG can also be seen.

Osteoporosis Most common bone disease in adults, especially in old age Much more common in females than males Defined by a decrease in “bone mineral density” Osteoblast activity less than normal, due to : Lack of physical stress (sedentary lifestyle, lack of exercise) Malnutrition (insufficient protein matrix formation) Lack of vitamin C (collagen synthesis) Postmenopausal lack of oestrogen (oestrogen stimulates osteoblast activity) Old age (general reduction in growth factors and protein synthesis) Treatments include bisphosphonates, calcium supplementation, Vitamin D, regular exercise program, oestrogen replacement)