Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism.

Abstract

Objectives To study whether fracture risk before and after surgery was increased in patients with primary hyperparathyroidism.

Design Cohort study.

Setting Three Danish university hospitals.

Participants 674 consecutive patients with primary hyperparathyroidism (median age 61, range 13-89 years) operated on during the period 1 January 1979 to 31 December 1997; 2021 age and sex matched controls from national patient register.

Main outcome measure Fractures.

Results The cases had an increased relative rate of fractures compared with the controls before surgery (1.8, 95% confidence interval 1.3 to 2.3) but not after surgery (1.0, 0.8 to 1.3). The risk of fracture was increased for the vertebrae (3.5, 1.3 to 9.7), the distal part of the lower leg and ankles (2.3, 1.2 to 4.3), and the non-distal part of the forearm (4.0, 1.5 to 10.6) before surgery but not after. The increase in risk of fracture began about 10 years before surgery. Risk peaked 5-6 years before surgery and remained raised, although at a lower level, in the five years immediately before surgery. A small increase in risk of fracture of the distal forearm emerged more than 10 years after surgery (2.9, 1.3 to 6.7).

Conclusions Risk of fracture is increased up to 10 years before surgery in patients with primary hyperparathyroidism. The risk returns to normal after surgery.

Introduction

Several studies have shown decreased bone mineral content or density in patients with primary hyperparathyroidism.[1 2] The reduction varied between skeletal regions,[1] generally tending towards a higher degree of cortical than trabecular bone loss. After surgical cure of primary hyperparathyroidism, the bone mineral density increases over the first few years in both the forearm[3-5] and the lumbar spine.[5 6] Although a deficit in bone mineral density in the forearm seems to remain,[3] spinal bone mineral density is usually restored.[6 7] Long term studies have found a permanent decrease in bone mineral density of the forearm in patients who had[7 8] and had not[9] had surgery. A follow up study comparing patients who had had surgery with patients who had not had surgery, showed no difference in forearm bone mineral content after 17 years despite an initial increase in forearm bone mineral content after surgery.[3] Both groups had lower forearm bone mineral content than control subjects.[3]

Decreased bone mineral density increases the risk of fracture. Several studies have reported an increased prevalence of fractures in patients at the time of diagnosis of primary hyperparathyroidism.[10-13] The sites at which risk of fracture is increased are the forearm,[12 13] the spine,[12 14] and the femoral neck.[12] Melton et al reported an increase in fracture risk before, but not after, diagnosis of primary hyperparathyroidism.[11] In contrast, a large cohort study found no increased risk of hip fractures.[15] Wilson et al also found no increased risk of vertebral fractures in patients with mild asymptomatic primary hyperparathyroidism.[2] However, most studies have reported on a limited number of patients[10 11] or have not evaluated the incidence of fracture before and after treatment.[10 12 13 15 16]

We conducted a large cohort study in 674 patients who had had surgery for primary hyperparathyroidism at three Danish centres and included 2021 controls to assess the risk of fracture before and after surgery at multiple skeletal sites.

Participants and methods

A total of 674 patients had had surgery for primary hyperparathyroidism during the period 1 January 1979 to 31 December 1997 at three Danish centres: Rigshospitalet in Copenhagen (1991-7), Aarhus University Hospital (1979-97), and Odense University Hospital (1979-90). The diagnosis was established by biochemical tests (raised serum concentrations of parathyroid hormone and calcium) at the regional laboratory and confirmed by histological examination of removed tissue at the regional institute of pathology in collaboration with the surgeon. Data on weight of removed tissue and histological diagnosis were retrieved from the medical files. As serum calcium concentration was measured by different methods at the three centres, serum calcium concentration was expressed as ionised serum calcium measured on the day before surgery. We used the formula

ionised serum calcium (mmol/l) = 0.25 + 0.45x serum total calcium (mmol/l).

For each of the 674 patients up to three matched control subjects were drawn from population lists of subjects who had …