Reduced Fracture Incidence in Patients Having Surgery for Primary Hyperparathyroidism

Martin Nilsson; Elin Ståhl; Kristina E Åkesson; Mark Their; Erik Nordenström; Martin Almquist; Anders Bergenfelz

Disclosures

Clin Endocrinol. 2022;97(3):276-283. 

In This Article

Abstract and Introduction

Abstract

Objective: The indication of surgery in primary hyperparathyroidism has been controversial, as many patients experience mild disease. The primary aim was to evaluate fracture incidence in a contemporary population-based cohort of patients having surgery for primary hyperparathyroidism. The secondary aim was to investigate whether preoperative serum calcium, adenoma weight or multiglandular disease influence fracture incidence.

Design: A retrospective cohort study with population controls. Primary outcomes, defined by discharge diagnoses and prescriptions, were any fracture and fragility fracture, secondary outcomes were multiple fractures anytime and osteoporosis. Subjects were followed 10 years pre- and up to 10 years postoperatively (or 31 December 2015). Multiple events per subject were allowed. Fracture incidence rate ratios (IRRs) for patients pre- and postoperatively were tabulated and evaluated with mixed-effects Poisson regression. Secondary outcomes were evaluated using conditional logistic regression.

Patients: A Swedish nationwide cohort of patients having surgery for primary hyperparathyroidism (n = 5009) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery between 2003 and 2013 was matched with population controls (n = 14,983). Data were cross-linked with Statistics Sweden and the National Board of Health and Welfare.

Measurements: Preoperative serum calcium and adenoma weight at pathological examination.

Results: Patients had an increased incidence rate of any fracture preoperatively, IRR 1.27 (95% confidence interval: 1.11–1.46), highest in the last year before surgery. Fracture incidence was not increased postoperatively. Serum calcium, adenoma weight and multiglandular disease were not associated with fracture incidence.

Conclusions: Fracture incidence is higher in patients with primary hyperparathyroidism but is normalized after surgery.

Introduction

Primary hyperparathyroidism (pHPT) is one of the most common endocrine disorders requiring surgical intervention. Parathyroidectomy was performed on 15.5 per 100,000 inhabitants in Sweden in 2019.[1] pHPT is associated with complications ranging from secondary osteoporosis, fractures, urinary stones, cardiovascular events, cancer, excess mortality, gastrointestinal to neuropsychiatric symptoms.[2–4] Previous studies have, in various settings and subgroups, shown increased incidence of fractures and cardiovascular events in pHPT cohorts,[5–11] and reduced incidence after parathyroidectomy.[7,8] A recent meta-analysis demonstrated a twofold increase in fracture risk among patients with pHPT compared to controls.[12]

Since the 1970s, there has been a shift in the presentation of pHPT towards less advanced disease with lower levels of serum calcium and parathyroid hormone (PTH), as well as lower adenoma weight and fewer complications at diagnosis.[13–23] An almost eightfold decrease in adenoma weight and an absolute and relative reduction of severe skeletal disease (osteitis fibrosa cystica) has been demonstrated in a meta-analysis of surgical cases from the United States during the years 1930–2000.[17] This is most likely caused by automatized biochemical assays for calcium and PTH and a growing awareness of pHPT and hypercalcemia as causes of morbidity, although there also might be other explanations such as dietary supplementation of vitamin D and calcium.[17] Further, there is an underlying assumption that early intervention might prevent severe complications such as secondary osteoporosis, cardiovascular events, cancer and excess mortality.

The primary aim of this study is to investigate whether the reduced fracture incidence after surgery observed in previous studies can be demonstrated in a modern setting, in patients with less advanced disease compared to previously studied cohorts.[5–7,9,11] Secondly, we investigated if fracture incidence relates to disease severity, measured as serum calcium or adenoma weight at histopathology and to multiglandular disease. In addition, we studied the prevalence of osteoporosis and medications affecting bone metabolism in the cohort.

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