Metabolic disorders of bone
Osteomalacia
Osteomalacia is defective mineralization of bone due to metabolic causes such as vitamin D deficiency, renal disease, celiac disease, cystic fibrosis, hypophosphatemia, or medications (e.g., phenytoin, steroids, aluminum, fluoride). Osteoporosis is excluded from osteomalacia.
Symptoms are often non-specific and may include fatigue, muscle weakness, and an increased tendency to fractures.
Imaging may show characteristic Looser’s zones (pseudofractures), which appear as areas of increased lucency. These are more commonly seen in the femoral neck and pelvic bones. Bone density is decreased.
An iliac crest biopsy shows widened osteoid seams due to uncalcified bone matrix. Serum alkaline phosphatase is elevated.
Management focuses on correcting the underlying disorder and providing vitamin D and calcium supplementation.
Osteopetrosis
Osteopetrosis 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 the carbonic anhydrase enzyme.
Symptoms result from:
- Fractures
- Entrapment syndromes (e.g., cranial nerve palsies, deafness)
- Bone marrow involvement leading to severe anemia, bleeding, or infections
Radiographs show dense cortical bone, increased bone density, and an Erlenmeyer flask deformity. Acid phosphatase may be elevated.
Treatment includes management of complications, bone marrow or stem cell transplant, vitamin D, and gamma interferon.
Erlenmeyer flask deformity
- Typically seen on radiographs at the lower end of the femur as 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
| Disorders | Serum Ca | Serum Phosphate | Serum Alkaline Phosphatase | Urine Ca |
| Osteomalacia | Low | Low | High | Low |
| Osteoporosis | Normal | Normal | Variable | Normal |
| Osteopetrosis | Normal | Normal | High | Normal |
Osteitis deformans (Paget disease of bone)
Osteitis deformans (Paget disease of bone) is characterized by abnormal remodeling of bone. The underlying pathology is excessive bone resorption by osteoclasts followed by abnormal new bone formation. Varying lytic and sclerotic phases can be seen within the same bone.
It has been associated with viral infections such as RSV and paramyxoviruses. It is typically seen after age 40 and is more common in males of northern European ancestry.
Commonly involved bones include the flat bones of the skull, pelvis, vertebrae, and femur.
Clinical features may include bone pain, fractures, increased head size, headaches, hearing loss, and radiculopathy.
Complications include high-output cardiac failure, spinal stenosis, and Pagets 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 may show collagen breakdown products such as hydroxyproline.
Medical therapy includes bisphosphonates (e.g., alendronate, risedronate) and calcitonin. Surgical management is with arthroplasty.
Osteoporosis
Osteoporosis is characterized by decreased bone mass and disrupted bone microarchitecture. It is a quantitative (not qualitative) defect in bone mineralization. It is preceded by osteopenia (decreased bone density).
By definition, a lumbar DEXA scan with a T score between 12.5 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.
Osteoporosis is more common in women and may 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 of fractures. Common locations include the wrist, vertebral column, and hip.
Genetic polymorphisms in genes for the calcitonin receptor, estrogen receptor, type I collagen receptor, and vitamin D receptor are associated with osteoporosis.
DEXA scans are the most accurate test for diagnosis. X-rays may show thinned cortices, osteopenia, and deformities such as kyphosis and codfish vertebra.
On bone biopsy, tetracycline labeling is normal in osteoporosis, while it is abnormal in osteomalacia.
Medical management of osteoporosis includes vitamin D and calcium supplementation, bisphosphonates, hormone replacement therapy, calcitonin, raloxifene, teriparatide, and monoclonal antibodies such as 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, Gauchers 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