Bone metabolism and calcium homeostasis

Bone is a metabolically active tissue that undergoes constant remodeling. The major cells involved in the remodeling process are osteoclasts and osteoblasts. Bone metabolism is closely interrelated with the metabolism of calcium, which also involves the intestine and kidney. Calcium balance is hormonally regulated by parathyroid hormone, vitamin D metabolites and calcitonin.

1. Bone Metabolism and Calcium Homeostasis Ahmed Madni Ph.D. Student (HEC Indigenous Scholar) Supervisor: Dr. Waheed S. Khan (DCS, NIBGE)

2. Bone is the primary storage site of calcium in the body; thus, bone metabolism plays a critical role in maintaining normal calcium levels B one metabolism  is the complex sequence of bone turnover ( osteoclastogenesis ) and bone formation ( osteoblastogenesis ) Bone metabolism (and thus calcium levels) are primarily regulated by 3 hormones, namely, parathyroid hormone (PTH), vitamin D (calcitriol), and calcitonin Basic(s) 2

3. The total plasma calcium concentration is maintained between 2.2 and 2.60 mmol /L (8.8–10.4 mg/ dL ) Calcium exists in the circulation in three forms The ionized Ca2+ is the most important, physiologically active form ( 50% of total calcium) The majority of the remaining calcium, is protein bound , mainly to negatively charged albumin ( 40 % ) T he rest is complexed to substances such as citrate and phosphate ( 10 % ) Serum Calcium 3

4. Bone Remodeling Process Figure 1 Maintaining bone mass: the bone remodeling cycle. Resorption and formation of bone by osteoclasts and osteoblasts is coupled. The processes numbered 1-4 are set in a timeline in the central panel 4

5. Figure 2 Major hormones influencing calcium homeostasis. A decrease in plasma ionized calcium stimulates release of PTH; this promotes Ca2 + reabsorption from the kidney, resorption from bone, and absorption by the gut via increased production of 1,25(OH)2D3. As a result, plasma calcium increases. Conversely, an increase in plasma ionized calcium stimulates release of calcitonin, which inhibits reabsorption of calcium by the kidney and osteoclast-mediated bone resorption. Calcium Homeostasis 5

6. The parathyroid glands make a hormone called parathyroid hormone (also known as PTH or parathormone ), which stimulates the action of  osteoclasts  when the amount of  calcium  in the blood falls (the hormone causes the transfer of  calcium  from bone to blood) Vitamin D (calcitriol) is a long-term regulator of serum calcium, with a half life of around 6 hours. Its main function is to increase the intestinal absorption of calcium Calcitonin  is the  regulation  of  calcium  levels in your blood by inhibiting bone breakdown (resorption) by regulating the number and activity of osteoclasts and decreasing kidney reabsorption of  calcium Hormones 6

7. O steomalacia Hypercalcemia ( is a high calcium (Ca²⁺) level in the blood serum ) Hyperparathyroidism ( too much parathyroid hormone in the bloodstream ) Pseudohypoparathyroidism ( hypocalcemia, hyperphosphatemia, and increased concentrations of PTH(1–84) ) Disorders of Calcium M etabolism 7

8. Total Calcium – Measurement on most chemistry analyzers – spectrophotometric Free Calcium (ionized Calcium) – Better reflects Ca metabolism and status than Total – Biologically active and tightly regulated – Measured by ISE (ion selective electrode), generally ion-specific measurement of whole blood sample Laboratory Testing of Calcium 8

9. PTH – Immunoassay , usually sandwich type, for intact PTH – ALWAYS report with Ca level – Useful for differential diagnosis of hypercalcemia and hypocalcemia Vitamin D – Serum sample – 25-OH-D – immunoassay (RIA, EIA , ICMA) or LC-MS/MS (D2 and D3 and D3 epimer ) – 1,25-diOH-D – extraction, chromatography , RIA Laboratory Testing of PTH and Vitamin D 9

10. Thank you for your Kind Attention..