Metabolic disorders of bone

Osteomalacia

It is characterized by defective mineralisation of bone due to metabolic causes like Vit D deficiency, renal disease, celiac disease, cystic fibrosis, hypophosphatemia or medications like phenytoin, steroids, aluminum and fluoride etc. Osteoporosis is excluded from osteomalacia. It has non-specific symptoms like fatigue, muscle weakness, propensity to fractures etc. Imaging shows characteristic Looser’s zones which are pseudofractures and show increased lucency more commonly seen in femoral neck and pelvic bones. Bone density is decreased. Iliac crest biopsy shows widened osteoid seams due to uncalcified bone matrix. Serum alkaline phosphatase is elevated. Management depends on correcting the underlying disorder, Vit D and calcium supplementation.

Osteopetrosis

It is an inherited metabolic bone disease caused by failure of osteoclasts to resorb bone. It may be autosomal recessive or autosomal dominant. It can occur due to defects in chloride channels or carbonic anhydrase enzyme. Symptoms occur due to fractures, entrapment syndromes like cranial nerve palsies, deafness, and bone marrow involvement leading to severe anemia, bleeding or infections. Radiographs show dense cortical bone and increased bone density and Erlenmeyer flask deformity. Acid phosphatase may be elevated. Treatment includes management of complications, bone marrow or stem cell transplant, Vit D and gamma interferon.

Erlenmeyer flask deformity

• Typically seen in radiographs at the lower end of the femur as a flaring of the metaphysis
• Common causes include osteopetrosis, achondroplasia, bone dysplasias, lysosomal storage disease, sickle cell disease and thalassemia

Lab values in common metabolic disorders of the bone

Osteitis deformans (Paget disease of bone)

It is characterized by abnormal remodeling of bone. Excessive bone resorption by osteoclasts followed by abnormal new bone formation is the underlying pathology. Varying lytic and sclerotic phases are seen in the same bone. It has been associated with viral infections like RSV and paramyxoviruses. It is seen after the age of 40 years and is more common in males of northern European ancestry. It involves flat bones of the skull, pelvis, vertebrae and femur. It presents with bone pain, fractures, increase in head size, headaches, hearing loss, radiculopathy etc. Complications include high output cardiac failure, spinal stenosis and Paget’s sarcoma. Imaging shows radiolucent, lytic areas mixed with thick, sclerotic areas of bone, thick trabeculae and bowing of long bones. Serum alkaline phosphatase is elevated and urine shows collagen breakdown products like hydroxyproline. Medical therapy is with bisphosphonates like alendronate and risedronate and calcitonin. Surgical management is with arthroplasty.

Osteoporosis

It is a disease characterized by decrease in bone mass and disrupted bone microarchitecture. Osteoporosis is a quantitative, not qualitative defect in bone mineralization. It is preceded by osteopenia or decreased bone density. By definition, a lumbar DEXA scan with a T score between 1-2.5 standard deviations below the average for a healthy young woman is called osteopenia while a T score below 2.5 standard deviations is called osteoporosis. It is more common in women and can be primary or secondary. Primary osteoporosis can be post-menopausal or senile. Secondary osteoporosis can result from corticosteroids, hyperparathyroidism, malabsorption syndromes etc.

Osteoporosis increases the risk for fractures, common locations include wrist, vertebral column and hip. Genetic polymorphisms in the genes for calcitonin receptor, estrogen receptor, type I collagen receptor, and Vit D receptor are associated with osteoporosis. DEXA scans are most accurate for diagnosis. X rays will show thinned cortices, osteopenia, deformities like kyphosis and codfish vertebra. On bone biopsy, tetracycline labeling is normal in osteoporosis, while it is abnormal in osteomalacia. Medical management of osteoporosis is with vitamin D and calcium supplementation, bisphosphonates, hormone replacement therapy, calcitonin, raloxifene, teriparatide and monoclonal antibodies like denosumab.

Risk factors for osteoporosis

• Caucasian women, sedentary lifestyle, smoking, alcoholism, low body weight
• Vit D deficiency, malabsorption syndromes, liver disease, hyperthyroidism, type I DM, sarcoidosis, renal failure
• Phenytoin, corticosteroids, chemotherapy, antiretroviral therapy, heparin, thiazolidinediones, omeprazole, levothyroxine

Osteonecrosis (avascular or ischemic necrosis)

• Bone necrosis due to interruption in blood supply
• Causes include trauma, corticosteroids, alcoholism, smoking, sickle cell disease, leukemias, Gaucher’s disease, gout, HIV, RA, SLE, pancreatitis
• Common sites include head of femur, head of humerus, knee
• Presents with pain of affected joint, fractures
• May be missed on X ray, prefer MRI, bone scan
• Complications include arthritis
• Management includes NSAIDs, joint rest, physical therapy, corticosteroids, surgery includes core decompression surgery, arthroplasty, osteotomy, bone grafting and joint replacement