degenerative bone disease

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

The term “degenerative bone disease” is somewhat of a misnomer. There are a few conditions though where the bone does, in a sense, degenerate.

Osteoporosis is a disease in which bones become fragile and more likely to break. If not prevented or if left untreated, osteoporosis can progress painlessly until a bone breaks. These broken bones, or fractures, occur typically in the hip, spine, and wrist. It is important to understand that bone is not a hard and lifeless structure; it is, in fact, complex, living tissue. Our bones provide structural support for muscles, protect vital organs, and store the calcium essential for bone density and strength.

Because bones are constantly changing, they can heal and may be affected by diet and exercise. Until the age of about 30, you build and store bone efficiently. Then, as part of the natural aging process, your bones begin to break down faster than new bone can be formed. In women, bone loss accelerates after menopause, when your ovaries stop producing estrogen - the hormone that protects against bone loss.

Think of your bones as a bank savings account. There is only as much bone mass in your account as you deposit. The critical years for building bone mass are from prior to adolescence to about age 30. Some experts believe that young women can increase their bone mass by as much as 20 percent - a critical factor in protecting against osteoporosis.

Any bone can be affected, but of special concern are fractures of the hip and spine. A hip fracture almost always requires hospitalization and major surgery. It can impair a person's ability to walk unassisted and may cause prolonged or permanent disability or even death. Spinal or vertebral fractures also have serious consequences, including loss of height, severe back pain, and deformity.

Millions of Americans are at risk. While women are four times more likely than men to develop the disease, men also suffer from osteoporosis.

The next type of disease that might be considered a degenerative bone disease is Paget’s disease. Paget’s disease of bone is also known as osteitis deformans.

It is defined as a progressive focal disorder of bone remodeling, in which normal bone is removed and replaced with abnormal bone.

The disorder is initiated by the proliferation of abnormally large osteoclasts, which resorb bone at local affected sites. Resorption is followed by a variable, but often marked, increase in the formation of new bone that is architecturally disorganized.

Paget's disease of bone is estimated to occur in 2 to 3% of persons > 60 in the United States. The prevalence varies widely in different regions of the world. The relative risk is increased about sevenfold in first-degree relatives of patients with Paget's disease.

The etiology has not been established, but genetic factors and a paramyxovirus infection may be involved. A genetic locus for susceptibility to Paget's disease has been identified on chromosome 18q in some large kindreds of patients, but not all kindreds show this locus, suggesting genetic heterogeneity. Structures resembling viral nucleocapsids have been identified in pagetic osteoclasts, but the results of studies of viral RNA expression in pagetic bone are inconsistent.

Pagetic lesions may be single or multiple and can involve any part of the skeleton, most commonly the pelvis, femur, spine, skull, and tibia. Pagetic osteoclasts are large and have many more nuclei than normal. Similarly, the osteoblastic response is exuberant and disorganized, producing "mosaic" bone with a woven pattern of collagen deposition. The adjacent marrow is vascular and often shows fibroblastic proliferation and decreased hematopoiesis. The hypercellularity may diminish, leaving sclerotic bone with little cellular activity, the so-called "burned-out" phase of Paget's disease. Frequently, all phases of the pagetic process occur simultaneously in a patient or even in a single lesion.

Patients may be asymptomatic for many years. Deformities, neurologic impairment, pathologic fractures, bone pain, hypervascularity, and arthritic changes in adjacent joints may be the initial symptoms. Changes in the skull often lead to impaired central nervous system function, particularly hearing loss due to involvement of the petrous bone. Involvement of the base of the skull may produce platybasia and basilar invagination, which leads to the rare, but serious, complication of brain stem compression. Vertebral deformity may lead to spinal cord compression. Although pagetic long bones often show increased density, their irregular structure leads to skeletal deformity with fragility and increased risk of fracture. The bone deformity can lead to damage to articular cartilage with consequent osteoarthritis, especially in the knee and hip. The hypervascularity of pagetic bone may produce palpable local warmth, increase cardiac output, and aggravate coexisting heart disease. Angioid streaks in the retina may occur but rarely impair vision.

Neoplastic changes in pagetic bone probably occur in < 1% of patients; however, osteosarcoma in the elderly is often associated with Paget's disease. Fibrosarcoma and chondrosarcoma may also occur. Such tumors may result in pathologic fractures. Benign giant cell tumors, which are called reparative granulomas or osteoclastomas, can also occur adjacent to pagetic lesions.

The increased incidence of primary hyperparathyroidism among patients with Paget's disease may be real or may be due to more intense investigation by the metabolic bone disease clinics to which these patients are referred. Hypercalcemia, while uncommon, occurs in immobilized patients with Paget's disease or may be caused by associated hyperparathyroidism; thus, patients with Paget's disease who require immediate bed rest should be monitored. Hypercalciuria, hyperuricemia, and gout occur more frequently in patients with Paget's disease, but the incidence of renal calculi does not seem to be much increased.

Asymptomatic Paget's disease may be detected incidentally by finding that the serum alkaline phosphatase level is elevated or that a suggestive x-ray abnormality is present. Further evaluation consists of a measurement of bone resorption and a bone scan. Measurement of urinary hydroxyproline can be helpful, but measurement of the new resorption markers, such as the N-telopeptide cross-links of collagen, is equally sensitive and is not affected by collagen in the diet. Increased uptake on bone scan is not diagnostic but indicates the sites at which x-rays should be obtained; it is particularly useful in differentiating degenerative joint disease from pagetic lesions. Serum calcium levels should be measured; hyperparathyroidism appears to be more common in patients with Paget's disease.

X-ray lesions may be largely osteolytic, osteoblastic, or mixed. The initial osteolytic lesion in the skull, termed osteoporosis circumscripta, may be followed by a marked increase in bone formation, ultimately leading to a thickened calvaria with an irregular "cotton wool" appearance. Bowing is common in affected limbs, and kyphosis occurs in patients with vertebral lesions.

Patients who develop osteosarcoma, fibrosarcoma, or chondrosarcoma have a grave prognosis and respond poorly to chemotherapy. However, benign giant cell tumors can be sensitive to glucocorticoids and antiosteolytic drugs such as bisphosphonates and calcitonin.

Localized asymptomatic disease requires no treatment. Treatment should be given, however, to those at risk of complications, including those with demonstrable osteopenia or osteoporosis and those whose disease affects weight-bearing sites (eg, long bones, vertebrae) or sites where neurologic damage is likely to occur. Severe deformities, neurologic symptoms, and degenerative joint changes in patients with more advanced disease are frequently irreversible. However, treatment can slow or prevent further deterioration.

Patients can be followed with serum alkaline phosphatase measurements for biochemical remission, but measurements of urinary collagen cross-link excretion may be more sensitive for early detection of relapse. In general, treatment should be continued until a biochemical remission has occurred, although remission cannot always be achieved in severe cases.

Hearing loss is common in patients with Paget's disease and should be monitored. The process probably cannot be reversed by treatment, but antiresorptive therapy may prevent progression.

Bisphosphonates are the therapy of choice. Newer bisphosphonates have replaced etidronate, which often produces only partial remissions and, if used in high doses, can impair mineralization, leading to osteomalacia. Pamidronate is available in the USA only for IV therapy. Doses of 30 to 90 mg are given in a single 4- to 6-hour IV infusion, which may be repeated at weekly or monthly intervals until biochemical remission is achieved. In patients with mild or limited disease, a single IV infusion may produce a prolonged remission. Oral alendronate 40 mg/day for 6 months frequently produces a prolonged remission. Shorter courses may be effective in milder cases. Risedronate 30 mg/day po may be given initially for 2 months. This drug produces a prolonged remission more often than etidronate does.

Salmon calcitonin injections 50 to 100 U/day have been widely used. This regimen heals osteolytic lesions, but adverse effects (eg, nausea and vomiting, flushing, local discomfort at the site of injection) are common, and resistance may develop.

Patients with severe deformities and irreversible osteoarthritic changes in the hip or knee joint may be treated surgically. Hip and knee replacements can be successful. Osteotomies can relieve nerve compression.

Intake of calcium and vitamin D should be adequate to prevent impairment of mineralization in bone that is turning over rapidly and to help reduce the rate of bone remodeling. Antiarthritic drugs should be used in patients with joint involvement in whom pain often persists despite biochemical remission.

A recent article discussed the role of pain in both degenerative bone as well as degenerative joint disease.

Pain. 2003 Oct;105(3):387-92.

Causes of pain in degenerative bone and joint disease: a lesson from vertebroplasty.

Center for Pain Medicine, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. davidniv@tasmc.health.gov.il

Pain in degenerative bone and joint disease is usually attributed to sensitized nociceptors in inflamed periarticular soft tissues. Here we draw attention to the potential contribution of intrinsic bone innervation. The structure and innervation of articular bone ends is analogous to that of teeth. Although some dental pain derives from inflamed periodontal soft tissue, a more important source is the dentine and root canal. By analogy, pain on weight bearing in osteoarthritis and related conditions may be due to compressive forces applied to the innervation of subchondral bone exposed by erosion of the overlying cartilage. Pain relief obtained by injecting acrylic cement into the bone interior during percutaneous vertebroplasty is consistent with this concept. The development of a new family of pain relief options based on "marrow canal treatment" may be a realistic possibility.

Degenerative bone disease