70  Calcium and Bone Metabolism

Published

October 5, 2025

70.1 Introduction

Calcium and bone metabolism form a vital part of paediatric growth and development. Bones are not static structures; they are dynamic organs that undergo continuous remodeling, with bone formation and resorption occurring simultaneously. This dynamic process depends heavily on an intricate balance between calcium homeostasis, hormonal regulation, and adequate nutrition.

Calcium is not only essential for skeletal integrity but also for neuromuscular function, blood coagulation, and intracellular signaling. Disturbances in calcium or bone metabolism can lead to conditions such as rickets, osteopenia, hypocalcaemia, or hypercalcaemia — all of which are relatively common in paediatric practice in Ghana and sub-Saharan Africa.

Understanding calcium and bone metabolism is fundamental for diagnosing and managing paediatric metabolic bone disorders, especially given the high burden of nutritional rickets and vitamin D deficiency observed in resource-limited settings.

70.2 Overview of Bone Structure and Function

Bone serves multiple physiological roles:

  • Structural support and protection for internal organs.
  • Reservoir for minerals, mainly calcium and phosphate.
  • Site of haematopoiesis within the bone marrow.
  • Endocrine organ, influencing energy metabolism through osteocalcin secretion.

Bone tissue consists of:

  • Organic matrix (osteoid): Composed mainly of type I collagen, providing tensile strength.
  • Inorganic mineral component: Primarily calcium hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂], which gives hardness and rigidity.
  • Cells: Including osteoblasts (bone-forming), osteoclasts (bone-resorbing), and osteocytes (mature cells embedded in bone).

The balance between bone formation and resorption maintains bone mass and structural integrity. This balance is regulated by both systemic hormones and local cytokines.

70.3 Calcium Homeostasis

70.3.1 Distribution of Calcium

Approximately 99% of total body calcium is stored in the skeleton and teeth. The remaining 1% is distributed in extracellular and intracellular compartments.

Compartment Approximate percentage Form
Bone and teeth 99% Hydroxyapatite crystals
Extracellular fluid 1% Ionized (50%), protein-bound (40%), complexed (10%)

Ionized calcium is the physiologically active form that participates in neuromuscular and enzymatic processes.

70.3.2 Normal Serum Calcium Levels

  • Total calcium: 2.1–2.6 mmol/L
  • Ionized calcium: 1.1–1.3 mmol/L

These levels vary slightly with age, protein status, and acid-base balance.

70.3.3 Sources and Absorption of Calcium

70.3.3.1 Dietary Sources

  • Breast milk: Primary source in infancy, though low in calcium, it is highly bioavailable.
  • Cow’s milk, fish with bones (e.g., sardines), green leafy vegetables (kontomire), and fortified foods are important dietary sources in Ghana.

70.3.3.2 Absorption

  • Occurs mainly in the duodenum and proximal jejunum.
  • Facilitated by active transport (vitamin D-dependent) and passive diffusion.
  • Factors enhancing absorption:
    • Adequate vitamin D.
    • Acidic gastric pH.
    • Presence of lactose in infants.
  • Factors reducing absorption:
    • Phytates (in cereals), oxalates (in spinach), and high phosphate intake (soft drinks).
    • Chronic diarrhoeal diseases or fat malabsorption.

70.4 Hormonal Regulation of Calcium and Phosphate Metabolism

Calcium balance is maintained by a homeostatic triad involving:

  1. Parathyroid hormone (PTH)
  2. Vitamin D (calcitriol)
  3. Calcitonin

These hormones act on the bone, kidney, and gastrointestinal tract to regulate calcium and phosphate concentrations.

70.4.1 Parathyroid Hormone (PTH)

70.4.1.1 Source

Secreted by the chief cells of the parathyroid glands.

70.4.1.2 Stimulus

Released in response to low serum ionized calcium.

70.4.1.3 Actions

  • Bone: Stimulates osteoclast-mediated bone resorption, releasing calcium and phosphate.
  • Kidney:
    • Increases calcium reabsorption in distal tubules.
    • Decreases phosphate reabsorption (phosphaturia).
    • Enhances 1α-hydroxylase activity → increases active vitamin D production.
  • Intestine: Indirectly increases calcium absorption via vitamin D activation.

70.4.1.4 Net Effect

Raises serum calcium and lowers serum phosphate.

70.4.2 Vitamin D (Calcitriol)

70.4.2.1 Sources

  • Endogenous synthesis: From 7-dehydrocholesterol in the skin upon exposure to sunlight (UVB rays).
  • Dietary intake: From fish oil, fortified milk, eggs, and supplements.

70.4.2.2 Metabolism

  1. Liver: Converts cholecalciferol to 25-hydroxyvitamin D [25(OH)D].
  2. Kidney: Converts 25(OH)D to 1,25-dihydroxyvitamin D [1,25(OH)₂D], the active form.

70.4.2.3 Actions

  • Intestine: Increases absorption of calcium and phosphate.
  • Bone: Promotes mineralization and bone formation.
  • Kidney: Facilitates calcium reabsorption.

70.4.2.4 Net Effect

Increases both serum calcium and phosphate.

70.4.2.5 Ghanaian Context

Children in Ghana should theoretically have adequate vitamin D due to abundant sunlight. However, urbanization, use of sunscreen, indoor lifestyles, dark skin pigmentation, and maternal deficiency during pregnancy contribute to suboptimal vitamin D levels in both mothers and infants. Consequently, nutritional rickets remains prevalent in some communities, particularly among exclusively breastfed infants without supplementation.

70.4.3 Calcitonin

70.4.3.1 Source

Secreted by parafollicular (C) cells of the thyroid gland.

70.4.3.2 Actions

  • Inhibits osteoclastic bone resorption.
  • Promotes renal calcium excretion.

70.4.3.3 Net Effect

Lowers serum calcium levels — physiologically less significant in children compared to adults.

70.5 Bone Remodeling

Bone is constantly renewed through remodeling cycles, which consist of:

  1. Activation: Recruitment of osteoclasts to resorption sites.
  2. Resorption: Breakdown of mineral and matrix by osteoclasts.
  3. Reversal: Transition phase.
  4. Formation: Osteoblasts lay down new osteoid, which becomes mineralized.

During childhood and adolescence, bone formation exceeds resorption, resulting in net bone gain. Peak bone mass is achieved around the third decade of life, after which bone loss begins gradually.

Factors influencing bone remodeling include:

  • Mechanical stress: Weight-bearing stimulates bone formation.
  • Hormones: Growth hormone, PTH, sex steroids.
  • Nutrients: Calcium, phosphate, magnesium, and vitamin D.
  • Cytokines: IL-1, TNF-α, and RANKL/OPG pathway.

70.6 Disorders of Calcium and Bone Metabolism in Children

70.6.1 Hypocalcaemia

70.6.1.1 Causes

  • Neonatal:
    • Prematurity.
    • Maternal diabetes.
    • Birth asphyxia or sepsis.
    • Hypoparathyroidism or pseudohypoparathyroidism.
  • Childhood:
    • Vitamin D deficiency (nutritional rickets).
    • Chronic renal disease.
    • Hypomagnesaemia.
    • Malabsorption syndromes.

70.6.1.2 Clinical Features

  • Tetany (carpopedal spasm, laryngospasm).
  • Seizures.
  • Paresthesiae.
  • Chvostek’s and Trousseau’s signs.
  • Irritability or poor feeding in infants.

70.6.1.3 Management

  • Acute: IV calcium gluconate (0.5–1 mL/kg of 10% solution).
  • Chronic: Oral calcium and vitamin D supplementation.
  • Treat underlying cause (e.g., magnesium deficiency).

70.6.2 Hypercalcaemia

70.6.2.1 Causes

  • Iatrogenic (excess vitamin D or calcium).
  • Primary hyperparathyroidism (rare in children).
  • Malignancy (leukaemia, lymphoma).
  • Granulomatous diseases (sarcoidosis, tuberculosis).
  • Prolonged immobilization.

70.6.2.2 Clinical Features

  • Nausea, vomiting, constipation.
  • Polyuria, polydipsia.
  • Lethargy, confusion.
  • Renal calculi or nephrocalcinosis.

70.6.2.3 Management

  • Adequate hydration.
  • Loop diuretics (furosemide).
  • Corticosteroids for vitamin D-related causes.
  • Bisphosphonates in refractory cases.

70.6.3 Rickets and Osteomalacia

70.6.3.1 Definition

Defective mineralization of bone matrix, leading to soft and deformed bones in children (rickets) and adults (osteomalacia).

70.6.3.2 Causes

  • Nutritional vitamin D deficiency: Most common in Ghana.
  • Calcium deficiency: Seen in diets low in dairy or with high phytate content.
  • Chronic kidney disease: Renal rickets.
  • Genetic: Vitamin D–dependent or resistant rickets.

70.6.3.3 Clinical Features

  • Delayed closure of fontanelle.
  • Frontal bossing, rachitic rosary.
  • Bowed legs (genu varum) or knock knees (genu valgum).
  • Widened wrists and ankles.
  • Growth retardation.

70.6.3.4 Investigations

  • Low calcium and phosphate.
  • Elevated alkaline phosphatase.
  • Low 25(OH) vitamin D.
  • Radiographs: Cupping and fraying of metaphyses.

70.6.3.5 Management

  • Vitamin D supplementation (2,000–6,000 IU daily for 3 months, then maintenance).
  • Dietary calcium supplementation.
  • Adequate sunlight exposure.
  • Health education for caregivers.

70.6.3.6 Local Note

Studies from Ghana and Nigeria have shown a mixed calcium and vitamin D deficiency pattern in rickets. Exclusive reliance on sunlight exposure without dietary correction may therefore be inadequate.

70.6.4 Osteopenia and Osteoporosis of Prematurity

70.6.4.1 Definition

Reduced bone mineral content in preterm infants due to inadequate mineral accretion.

70.6.4.2 Causes

  • Prematurity (most calcium accretion occurs in the third trimester).
  • Prolonged parenteral nutrition.
  • Chronic diuretic or steroid use.
  • Limited physical activity.

70.6.4.3 Prevention and Management

  • Adequate calcium and phosphate supplementation in preterm feeds.
  • Use of fortified breast milk.
  • Gentle physical therapy.

70.6.5 Renal Osteodystrophy

70.6.5.1 Pathophysiology

Chronic kidney disease leads to: - Impaired phosphate excretion (hyperphosphataemia), - Reduced calcitriol production, - Secondary hyperparathyroidism, - Bone demineralization and deformities.

70.6.5.2 Management

  • Dietary phosphate restriction.
  • Phosphate binders.
  • Active vitamin D analogues (calcitriol).
  • Correction of metabolic acidosis.

70.7 Laboratory Evaluation of Bone and Calcium Metabolism

Test Interpretation Clinical Utility
Serum calcium (total/ionized) ↓ in hypocalcaemia, ↑ in hypercalcaemia Basic screen
Serum phosphate ↓ in rickets, ↑ in renal disease Assess phosphate balance
Alkaline phosphatase (ALP) Elevated in bone formation or rickets Marker of bone turnover
Parathyroid hormone (PTH) High in secondary hyperparathyroidism Helps classify calcium disorders
25(OH) vitamin D Reflects vitamin D stores Deficiency common in rickets
1,25(OH)₂D Active form; low in renal disease Used selectively
Urinary calcium and phosphate To assess renal losses Useful in metabolic bone diseases

Radiologic investigations (wrist or knee X-rays) complement biochemical findings in rickets and other bone disorders.

70.8 Nutritional Considerations and Public Health Implications

In Ghana, dietary calcium intake among children is often below recommended levels, particularly in rural communities where milk consumption is limited. Staple diets based on maize, millet, and cassava have high phytate content, reducing calcium bioavailability.

Strategies to improve calcium and vitamin D status include: - Promoting exclusive breastfeeding with appropriate maternal nutrition. - Fortification of complementary foods with calcium and vitamin D. - Encouraging outdoor play for sunlight exposure. - Supplementation programs for at-risk groups (infants, adolescents, pregnant women).

Public health campaigns should also emphasize the dangers of excessive soda intake, as phosphoric acid in carbonated drinks can impair calcium absorption.

70.9 Summary

  • Calcium and phosphate metabolism is tightly regulated by PTH, vitamin D, and calcitonin.
  • The skeleton serves as the main calcium reservoir, undergoing constant remodeling.
  • Disorders such as rickets, hypocalcaemia, and renal osteodystrophy are common in paediatric practice.
  • Nutritional deficiency, limited sunlight exposure, and chronic kidney disease are leading causes in Ghana.
  • Early diagnosis, supplementation, and community education are vital for prevention and management.

70.10 Further Reading

  1. Thacher TD, Fischer PR. Vitamin D and calcium deficiencies in children living in tropical areas. Int J Vitam Nutr Res. 2013;83(5):292–301.
  2. Oduro-Boatey C, Aryeetey R, et al. Nutritional rickets among Ghanaian children: prevalence and associated dietary factors. Ghana Med J. 2020;54(2):78–85.
  3. Pettifor JM. Nutritional rickets: deficiency of vitamin D, calcium, or both? Am J Clin Nutr. 2004;80(6 Suppl):1725S–1729S.
  4. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281.
  5. Weaver CM, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development. Osteoporos Int. 2016;27:1281–1386.
  6. WHO. Guidelines on Vitamin D Supplementation for Infants and Children. Geneva: World Health Organization; 2019.
  7. Ghana Health Service. Nutrition and Micronutrient Guidelines for Child Health in Ghana. Accra: GHS; 2021.
  8. Kliegman RM, et al. Nelson Textbook of Pediatrics. 21st ed. Elsevier; 2020. Chapter on Calcium and Bone Metabolism.