CHAPTER 69
Metabolic Bone Diseases
Introduction
• Metabolic bone diseases are characterized by abnormal bone mineralization and growth.
• In the growing child, failure of bone mineralization leads to
— Growth plate widening and disorganization of the chondrocytes, with loss of the normal straight-columned orientation (eg, rickets)
— Accumulation of unmineralized osteoid in the trabecular bone of the metaphyses (osteomalacia)
• In skeletally mature adolescents, failure of bone mineralization leads to osteomalacia without rickets.
• Demineralized bone is less resistant to stress and may lead to long bone bowing and fracture.
Rickets
INTRODUCTION/ETIOLOGY/EPIDEMIOLOGY
• Rickets, the most common metabolic bone disease, is a failure of bone mineralization at the growth plate associated with a deficiency of calcium (hypocalcemic rickets) or phosphorous (hypophosphatemic rickets).
• Failure occurs during periods of rapid growth at a time when skeletal tissues require high levels of calcium and phosphate.
• Rickets is clinically apparent toward the end of the first year after birth, commonly identified because of tibial bowing and short stature. Deformities of the wrist and chest wall tend to develop later in childhood if rickets is not treated.
• It may be classified according to etiology (Table 69-1).
— Inadequate dietary intake of vitamin D, calcium, or phosphorous
■Rare in developed countries because calcium and phosphorous are found in milk and green vegetables
■A resurgence of rickets has been reported in nearly all developing countries.
■Occurs in breastfed neonates and infants because human milk is low in vitamin D
■Occurs because of atypical diets with no milk products (eg, vegetarian, lactose intolerant)
— Inadequate sunlight exposure (for skin conversion of vitamin D to an active form)
■Occurs in dark-skinned neonates and infants
Table 69-1. Etiologies of Rickets
| Etiology of Rickets | Distinguishing Features |
|---|---|
| Increased renal excretion | |
| X-linked hypophosphatemic rickets | Do not have tetany, myopathy, rachitic rosary, or Harrison groove; rarely have enamel defects Waddling gait and smooth (rather than angular) bowing of the lower extremities Hypertension and left-side ventricular hypertrophy possible Family history of similar bony deformities Laboratory values: very low serum phosphorous, normal serum calcium, normal PTH, high alkaline phosphatase, normal calcidiol, normal or low calcitriol, high urinary phosphorus |
| HHRH | Hypophosphatemia is mild in some cases, without signs of bone disease Nephrocalcinosis, nephrolithiasis Family history of similar signs and symptoms Laboratory values: very low serum phosphorous, normal serum calcium, normal or low PTH, high alkaline phosphatase, normal calcidiol, high calcitriol, high urinary calcium |
| Renal insufficiency | Laboratory value: elevated creatinine |
| McCune-Albright syndrome | Café au lait spots; liver disease; hyperthyroidism; Cushing syndrome; fibrous dysplasia in long bones, ribs, and skull; precocious puberty; advanced skeletal maturity |
| Fanconi syndrome | Polyuria, polydipsia, dehydration, glycosuria, phosphaturia, proteinuria, hypokalemia, hyperchloremic metabolic acidosis |
| Diuretic medications (eg, furosemide) | |
| Renal tubular acidosis with hypercalciuria | |
| Renal tubular dysfunction (eg, cystinosis, tyrosinemia, galactosemia, fructose intolerance, Wilson disease, lead poisoning, other heavy metal poisoning) | |
| Tumors (usually a small, benign mesenchymal tumor) | Laboratory values: very low serum phosphorous, low calcitriol Imaging studies: positive MRI or indium 111 scan |
| Dietary | |
| Inadequate calcium intake | |
| Inadequate phosphate intake (rare; but can occur in infants on elemental formula) | |
| Inadequate vitamin D intake (deficient milk products or exclusively breastfed) | |
| Poor absorption from GI tract | |
| Lack of sunlight exposure | |
| Defect in renal enzyme (1α-hydroxylase) that converts calcidiol to calcitriol, the active metabolite (vitamin D pseudodeficiency) | Family history of similar bony deformities Laboratory values: low or normal serum phosphorous, low serum calcium, high PTH, very high alkaline phosphatase, normal calcidiol, very low calcitriol, low urinary calcium |
| End-organ resistance to effect of calcitriol (Vitamin D–resistant rickets) | Family history of similar bony deformities Laboratory values: low or normal serum phosphorous, low serum calcium, high PTH, very high alkaline phosphatase, normal calcidiol, very high calcitriol, low urinary calcium |
| High phytin formula (eg, soy) | |
| Antacids that contain aluminum (which binds dietary phosphates, preventing absorption) | |
| Anticonvulsants that accelerate calcidiol metabolism (eg, phenytoin, phenobarbital) | |
| Gastrectomy (total or partial) | |
| Short gut syndrome | |
| Hepatic insufficiency or disease | Laboratory value: elevated liver enzymes |
| Fat malabsorption (eg, cystic fibrosis, celiac or inflammatory bowel disease) | Steatorrhea |
| Chronic pancreatic insufficiency | Steatorrhea |
