Clinical Vignette: Natural History of Untreated Paget's Disease of the Tibia

In 1987, a 68-year-old white woman presented with monostotic Paget's disease of the left tibia first diagnosed incidentally in the late 1950s. At initial diagnosis she had no symptoms, but she reported that in recent years she had noticed dull aching in the tibial shaft as well as episodes of left knee pain. Measurements of serum alkaline phosphatase in the past had ranged from mildly above normal to twice the upper limit of normal. She had never received treatment with a bisphosphonate or calcitonin. However, her primary care physician had obtained radiographs of her tibia over the years, and the progression of her disease in the absence of any treatment can be seen in Figure A, an anteroposterior view, and Figure B, a lateral view of the left lower leg. In the 1962 and 1964 radiographs, there is cortical thickening (arrows) and (in 1964) early anterior bowing, changes typical of Paget's disease; the distal tibia is uninvolved. By the later films (1976 and 1987), there is distal progression with involvement of the entire tibia, further expansion and increased size of the bone, and marked progression of the deformity with increasing anterior bowing; in the 1987 X-ray, there is also obvious lateral bowing and narrowing of the joint space at the knee. Paget's disease of bone is the result of a localized increase in bone remodeling initiated by increased numbers of larger than normal osteoclasts at affected skeletal sites. Increased bone resorption at those sites is followed by a compensatory increase in new bone formation, producing bone that is architecturally altered and structurally inferior. This may lead, depending on the location, to bone deformity, fracture, secondary osteoarthritis, or neurological compromise.1 Recent progress in the treatment of Paget's disease has occurred with the availability of potent new bisphosphonates, such as pamidronate and alendronate, which have the potential to restore pagetic bone turnover to normal levels in a majority of patients.2, 3 Biopsies of pagetic bone reveal normal lamellar deposition at sites of new bone formation following effective treatment.4 Although it is not proven that arrest of the pagetic remodeling abnormality will prevent clinical progression and future complications, two messages are clear. First, failure to treat can be associated with progressive deformity and evolution of symptoms as shown in this patient. Second, effective medical treatment with restoration of normal remodeling is associated with the formation of histologically normal bone. Thus, we recommend treating Paget's disease even in the asymptomatic patient if the process is active (i.e., elevated indices of bone turnover are present) at sites such as the skull, spine, long bones, and areas adjacent to major joints (e.g., pelvis) where disease progression over time is likely to put the patient at risk of complications.