Differential Diagnosis: Bone Pain and Fractures

Summary

• Bone pain is a very common feature of many metabolic bone diseases, including metastatic bone disease, osteoporosis, and Paget’s disease of bone.

• The mechanism of pain is complex and depends on an increasing number of interrelated pathways and mediators.

• In general terms, bone pain can be categorized as arising from one a direct action on bone nociceptors or from a secondary mechanical effect.

• There is little evidence that bone loss itself causes symptoms until a fracture occurs. Therefore, in osteoporosis all the clinical manifestations are a direct or indirect consequence of fracture, and thus bone pain is the main clinical symptom.

• The most common causes of true bone pain, as opposed to joint pain, are trauma, osteoporosis, and malignancy.

• Distinguishing between these different causes can be difficult, and some diagnoses are often made only after exclusion of all other diseases. Pain due to acute vertebral fracture can be extremely severe and therefore difficult to manage.

• In the initial management, the aim is to reduce the level of discomfort and improve mobility as soon as possible. Immobilization should be avoided, since prolonged immobilization is associated with further bone loss.

• Simple analgesics are sometimes sufficient to alleviate the pain. In patients for whom simple analgesics do not provide adequate pain relief, NSAIDs or narcotic analgesics may be necessary.

• To date, a large number of clinical studies have shown that either salmon calcitonin or bisphosphonates (clodronate and pamidronate given parenterally) are effective in the management of acute stages of acute vertebral collapse. Both of these treatments are able to determine a significant shortening of the painful phase in osteoporotic patients, favoring a good and rapid recovery.

Bone pain is a very common feature of many metabolic bone diseases, including metastatic bone disease, osteoporosis, and Paget’s disease of bone. The bone pain that accompanies such diseases is often severe and debilitating. Attempts to relieve pain in these conditions can dominate the management of the overall disease. A common factor in many metabolic bone diseases is increased bone resorption, mediated by activated osteoclasts, a pathophysiologic process that often results in pain by a variety of direct and indirect mechanisms. The mechanism of pain is complex and depends on an increasing number of interrelated pathways and mediators. The sensation of pain from bone is understood poorly, although it is believed to depend mainly on the action of nociceptors in the periosteum and around joint surfaces; areas such as the cortex and bone marrow are believed to be insensitive to pain. In general terms, bone pain can be categorized as arising from a direct action on bone nociceptors or from a secondary mechanical effect. A number of chemical mediators can affect bone nociceptors directly, in addition to structural damage to nerve fibers by direct compression of tissue. Often, mechanical pressures on an area of bone that is insensitive may alter the shape of a nearby joint and cause pain. For instance, a vertebral compression fracture may distort a nearby apophyseal joint, triggering nociceptors and resulting in pain. Although the mechanisms of bone pain in a variety of different diseases may have common pathways, the role of certain mediators as a cause of pain may differ, which may have therapeutic implications. There is little evidence that bone loss itself causes symptoms until a fracture occurs, and a vertebral fracture can remain asymptomatic. It is perhaps this clinically silent nature of the disease that makes osteoporosis such a challenge. Therefore, in osteoporosis all the clinical manifestations are a direct or indirect consequence of fracture, and thus bone pain is the main clinical symptom.

There are both osseous and extra-osseous factors that contribute to fracture in patients with osteoporosis. Osseous factors include decreased skeletal mass, altered architectural orientation of skeletal structures, and reduced strength of the skeletal material. Extra-osseous factors include propensity to fall, poor reflex response to falling, and inadequate energy absorption by soft tissue at the point of impact. The relative contribution of each factor will vary from person to person as well as across the different fracture syndromes. Often, decreased mass is considered the single most important factor in most patients, but this may be because we have recognized it the longest and understand it the best. In clinical practice, non-specific bone pain is a very common complaint, the causes of which are extremely varied. In general, osteoporosis is not associated with back pain until a vertebral fracture has occurred. Even when a fracture has occured, many patients are without evident clinical symptoms. Osteoporotic vertebral fracture should always be considered within the differential diagnosis of any non-specific back pain. The most important diseases that cause bone pain are listed in Table 11.1.

The importance of reaching the correct diagnosis is self-evident, as some of the causes are invariably fatal while others can be treated easily but may be fatal if left untreated. A number of diseases affecting the musculoskeletal system, such as polymyalgia rheumatica, hypothyroidism, and Parkinson’s disease, may also produce symptoms resembling bone-originating pain. The most common causes of true bone pain, as opposed to joint pain, are trauma, osteoporosis, and malignancy. Distinguishing between these different causes can be difficult, and some diagnoses are made only after exclusion of all other diseases.