In growing children, a deficiency of vitamin D causes rickets while in adults (mostly women), osteomalacia results. Since bone abnormalities are the most important feature of rickets, a brief review of bone physiology is given first.

Vitamin D deficiency is now understood as a disorder of calcium–phosphate homeostasis due to deficiency of active vitamin D (calcitriol), leading to defective mineralization of osteoid rather than purely a dietary deficiency. It represents a failure of normal bone mineral deposition at the osteoid matrix due to impaired intestinal calcium and phosphate absorption and secondary hormonal adaptations (especially PTH elevation).

 Brief Physiology of Bone

Bone can be considered a specialized connective tissue made rigid by an orderly deposition of mineral crystals over an organic matrix. Bone fibers consist mainly of the protein ossein (now known to be type I collagen) encrusted with crystalline mineral. These fibers are embedded in an amorphous ground substance composed of proteoglycans (mucopolysaccharides), glycoproteins, and water, which regulate mineral deposition and provide structural organization. Two other proteins, osseomucoid and osseoalbuminoid, also occur in bone but to a lesser extent than ossein.

It is important to realize that bone is being continually destroyed and renewed through the process of remodeling. Thus, bony tissue is not inert and static but is highly dynamic, involving coordinated activity of osteoclasts (bone resorption) and osteoblasts (bone formation). This continuous turnover is essential for calcium homeostasis and structural integrity.

The chemical composition of fat-free bone is given below:

Water = 25%

Inorganic matter (chiefly Ca and P in a ratio of 2.2 : 1) = 45%

Organic matter (proteins and mucopolysaccharides) = 30% (in which 95% is ossein)

The inorganic fraction is composed of crystals forming hexagonal plates measuring about 50 × 10 μm, deposited in a highly ordered manner along and parallel to collagen fibrils. This arrangement provides maximum mechanical strength. The small size and flat surface of these crystals confer a very large surface area, allowing rapid ion exchange.

Bone crystals consist chiefly of hydroxyapatite, Ca₁₀(PO₄)₆(OH)₂, but they also contain carbonate, citrate, and small amounts of Na, Mg, Cl, and F. These substitutions influence crystal stability and solubility. The crystals are surrounded by a hydration shell which permits free exchange of ions between extracellular fluid and the interior of the crystals.

The total surface area of bone mineral in the human body is extremely large (estimated at 100 to 200 acres), highlighting the high metabolic activity of bone. Lead, strontium, and radium can replace calcium ions in the crystal lattice, while fluoride can replace hydroxyl ions, altering crystal properties and potentially affecting bone strength.

Modern addition: Bone mineral homeostasis is regulated by vitamin D (calcitriol), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), which together control intestinal absorption, renal excretion, and skeletal mobilization of calcium and phosphate. These hormones integrate bone with kidney and intestinal physiology to maintain serum calcium within a narrow physiological range.

 Bone Development

At the ends of long bones during normal growth, cartilage cells in the epiphyseal plate proliferate, mature, and eventually undergo hypertrophy and degeneration, after which they are replaced by osteoblasts. Capillaries invade this region forming the primary ossification center. Osteoblasts then lay down an osteoid matrix consisting of collagen and ground substance.

The osteoblasts also initiate mineralization by seeding crystals of calcium phosphate onto the osteoid framework. Mineral deposition is closely associated with cellular metabolism, including glycolysis and generation of phosphate-rich intermediates. Osteoblasts contain the enzyme alkaline phosphatase, which is essential for hydrolyzing organic phosphate esters and increasing local phosphate concentration required for mineral deposition.

Mineralization occurs when the product of serum calcium and phosphate concentration (Ca × Pi) exceeds a critical threshold, allowing precipitation of calcium phosphate. The initial amorphous calcium phosphate gradually transforms into mature hydroxyapatite crystals. Bone becomes progressively stronger through crystal growth, increased mineral density, and displacement of water from the matrix.

Modern addition: Mineralization occurs at the osteoid–mineral interface and requires adequate levels of calcium, phosphate, and active vitamin D. Failure of this process leads to accumulation of unmineralized osteoid, which is the fundamental lesion in both rickets (in children) and osteomalacia (in adults). Osteoblast activity may be normal or increased, but mineral deposition is defective.

 Rickets

It is a disease primarily due to deficiency of vitamin D, but inadequate dietary calcium, phosphate deficiency, and lack of sunlight exposure may also contribute.

Modern correction: Rickets results from deficiency of active vitamin D (calcitriol), which may occur due to low intake, inadequate sunlight exposure, malabsorption, liver disease, or chronic kidney disease (defective conversion to active form).

Rickets is associated with the following abnormalities:

As compared to normal bone, the rickety bone has less inorganic matter, and this decreased mineral content is the primary defect. The cartilage cells at the ends of long bones do not undergo normal degeneration but continue to proliferate and accumulate. Osteoblastic activity is usually increased, as shown by increased osteoid formation; however, mineralization of this osteoid is defective.

The epiphyseal plate, which normally is a thin cartilage zone, becomes markedly widened both laterally and in depth. This leads to irregular calcification and formation of nodules at costochondral junctions (rickety rosary) and at wrists, ankles, and knees. Characteristic skeletal deformities develop due to softening of growing bone under mechanical stress.

The tibia bends forwards (bow legs), the femur may bend outwards, and the spine shows kyphosis or scoliosis. A transverse groove may appear corresponding to the insertion of the diaphragm on either side of the thorax (Harrison’s sulcus). The sternum protrudes forward (pigeon chest). These chest deformities are clinically significant as they impair respiratory mechanics and reduce pulmonary compliance.

The forehead protrudes due to frontal bossing caused by overgrowth of unmineralized osteoid. Parietal bones may also show prominent bosses. The skull may show craniotabes (soft skull with delayed ossification), widening of sutures, and delayed fontanelle closure. Long bones such as humerus and forearm bones may become curved.

There is delayed eruption of teeth and defective enamel formation, increasing susceptibility to dental caries. Generalized muscle hypotonia and weakness are also present, contributing to abdominal protrusion (pot belly).

On chemical analysis, bones of rickety patients contain much less inorganic matter (Ca and P) and relatively more water compared to normal bones.

In rickets, serum calcium is usually normal or mildly reduced due to compensatory hormonal regulation, but serum inorganic phosphate is characteristically low (1–2 mg/dL vs normal 4–6 mg/dL). Secondary hyperparathyroidism plays a key role in phosphate loss through renal excretion.

The product of serum Ca × phosphate is clinically important: values above 40 generally prevent rickets, whereas values below 30 are associated with disease. Vitamin D therapy restores this balance by increasing intestinal absorption of calcium and phosphate and suppressing secondary hyperparathyroidism. The parathyroid glands show hyperplasia due to chronic stimulation.

Serum alkaline phosphatase activity is markedly increased and serves as an important diagnostic marker. This reflects increased osteoblastic activity attempting bone formation, although mineralization remains defective.

There is delayed dentition and defective enamel formation, predisposing to dental caries.
Early diagnosis is essential because established skeletal deformities may become irreversible. Characteristic radiological findings—cupping, fraying, and widening of metaphyses—appear before clinical deformities become obvious, enabling early detection.

 Osteomalacia or Adult Rickets

It occurs mostly in women who are economically poor and have undergone repeated cycles of pregnancy and lactation. Lactation imposes a greater mineral demand than pregnancy due to continuous calcium loss in breast milk.

In osteomalacia, there is defective mineralization of newly formed osteoid in mature bone. Bone minerals are mobilized, and calcium depletion occurs in both cortical and trabecular bone. The bone becomes softer than in rickets due to accumulation of unmineralized osteoid in already formed bone.

As bone softens, mechanical stress leads to bowing of long bones, vertical compression of vertebrae, and flattening of pelvic bones, narrowing the pelvic outlet. This results in a contracted pelvis, an important cause of obstructed labor.

Spontaneous fractures and vertebral collapse may occur due to reduced bone strength. Serum calcium may fall significantly, sometimes leading to hypocalcemic tetany due to neuromuscular excitability.

Osteomalacia is characterized clinically by diffuse bone pain, proximal muscle weakness (especially difficulty in climbing stairs or rising from sitting position), and radiologically by Looser’s zones (pseudofractures), which are characteristic incomplete fractures in areas of mechanical stress.