Dem Old Bones

By Peter Galvin, MD

An 80-year-old woman presented to the endocrinology clinic in Osaka, Japan with a several-year history of gradual forehead enlargement and hearing loss. She reported no headache or bone pain. Sixteen years earlier, mild thickening of the skull had been noted on imaging studies that had been performed to evaluate early-stage breast cancer, which was successfully treated. However, the patient had failed to follow up on the imaging findings as had been recommended. At the current presentation, physical examination was notable for frontal bossing (enlargement of the forehead – see Panel A). Her alkaline phosphatase level was 592 (reference range 38 to 113). Alkaline phosphatase is an enzyme found in many body systems including bone, liver, and bile ducts. Elevated levels can be seen in bone disorders, bile duct blockage, cirrhosis, and many other disorders.

Skull X-rays showed marked thickening of the calvarium (top of the skull) with irregular patches of sclerosis (bone thickening) and lucency, resulting in a “cottonwool” appearance (see Panel B). Whole body CT scanning showed no cancer but did show severe cortical thickening, sclerosis, and focal osteolysis (thinned bone) of the skull (Panel C). All bones have an outer layer of compact bone with an inner layer of spongy bone that contains bone marrow. The skull has two levels of compact bone with the spongy bone layer, or diploic area, in the middle. Note in Panel C that the middle, or diploic, part of the skull is markedly widened. Audiometry confirmed hearing loss. A nuclear bone scan (Panel D) showed increased bone activity in the skull and left pelvis – note these areas are darkened. A diagnosis of Paget’s disease of bone was made.

Paget’s disease of bone was first described by Sir James Paget in 1877. It should not be confused with Paget’s disease of the breast, which he described in 1874. The breast disease, which is exceedingly rare, involves the nipple and areola, which has an eczema-like rash that is red, itchy, and tingly, and over time, becomes flaky, scaly, and thickened. Paget’s disease of the breast is almost always a harbinger of breast cancer. Paget’s disease of bone, formerly called osteitis deformans, involves cellular remodeling and deformity of bones. There is excessive bone breakdown and disorganized new bone formation. All this bone activity raises the alkaline phosphatase level, as was seen in this case. There is also an increased risk of bone fracture, called a pathological fracture.

When Paget’s involves the skull, there is enlargement of the skull (hat size increases) and frontal bossing, also seen here. Hearing loss is common because the bony enlargement squeezes the auditory nerves that run through the auditory canal to the ears. In most cases, the cause of Paget’s is unknown, although there can be a hereditary link in some cases. Uncommonly, Paget’s can be caused by a viral infection such as RSV and measles. Treatment is normally with bisphosphonates, for example Fosamax, Didronel, Aredia, and Zometa which are used to treat osteoporosis. This patient was given a bisphosphonate and, over time, her alkaline phosphatase level decreased, but her frontal bossing and hearing loss did not change.

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