John P. Bilezikian*
In many parts of the world, primary hyperparathyroidism (PHPT) has become mainly an asymptomatic disease characterized by mild hypercalcemia and elevated levels of parathyroid hormone. In other parts of the world where PHPT is not detected readily in the population and/or where vitamin D deficiency is likely to be severe, the disease tends to be symptomatic with the adage of "bone, stones, and groans" being most apt. In such patients, radiological signs of PHPT with generalized bone loss, salt and pepper degranulation of the skull, distal tapering of the clavicle, and periosteal resorption of the phalanges are common. These features are described under the collective term, osteitis fibrosa cystica.
When patients present with mild hypercalcemia in the absence of symptoms, radiological manifestations tend to be most uncommon. In many series, the incidence of overt radiological bone disease in asymptomatic primary hyperparathyroidism is well under 5%. This observation, however, does not mean that these patients would not demonstrate bone involvement if sensitive quantitative measures were used. Indeed, by dual energy X-ray absorptiometry (DXA), bone loss is regularly seen. The pattern of bone loss is particularly noteworthy in that the predilection of parathyroid hormone to erode cortical bone leads to greater loss at the distal 1/3 of the radius (primarily a cortical site) and much less involvement at the lumbar spine (primarily a cancellous site). This pattern of bone involvement is even seen in postmenopausal women not taking estrogen replacement therapy. Since bone loss by DXA is a major feature of PHPT, guidelines for surgery in this disease include densitometric criteria.
According to the recent NIH Workshop on the Management of Asymptomatic Primary Hyperparathyroidism, a T-score of <-2.5 at any site (lumbar spine, hip, or distal radius) is a criterion for parathyroidectomy. This recommendation is based upon the assumption that bone loss in PHPT carries with it the same fracture risk at the same bone density as subjects with the same degree of bone loss who do not have PHPT. There are no data that address this point specifically in PHPT.
When other skeletal considerations are taken into effect, in fact, this assumption might be questioned. For example, in PHPT, bone geometry may be altered due to the fact that parathyroid hormone (PTH) stimulates periosteal bone deposition while it may erode cortical bone. Such a change in geometry, as shown in PHPT and when osteoporotic subjects are treated with PTH, would lead to an increase in bone strength due to biomechanical considerations. Furthermore, microarchitectural features of cancellous bone in asymptomatic PHPT favor a profile that tends to strengthen bone. Without actual fracture incidence data, therefore, it is hard to know what a T-score means in this disease. Nevertheless, until further data are available, the criteria set forth by the NIH panel are reasonable.
Finally, when subjects undergo successful parathyroidectomy, bone density improves remarkably at the lumbar spine and the hip. Smaller changes are seen at the distal radius. Similar to the reduction in bone density in PHPT and its uncertain relationship to fracture risk, it is not known whether increases in bone density after successful parathyroidectomy are associated with a reduction in fracture risk. Until more data are available, however, this assumption seems reasonable. Clearly, skeletal health is an important consideration both in the severe and the more mild forms of PHPT seen throughout the world today.
* Professor of Medicine, College of Physicians and Surgeons, Columbia University
New York , NY, USA