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
• Bone 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)
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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%)
• The rest is complexed to substances such as citrate and phosphate (10%)
Serum Calcium
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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
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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
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7. • Osteomalacia
• 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 Metabolism
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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
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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
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10. Thank you for your Kind Attention..