Reliability of parathyroid hormone measurements in the period immediately following hip fracture

Age and Ageing,  May, 1997  by Antony Johansen,  Mike D. Stone,  M. Sinead O'Mahony,  Helen Westlake,  J. Stuart Woodhead,  Ken W. Woodhouse

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Keywords: elderly patients, hip fracture, parathyroid hormone

Introduction

Patients presenting with hip fracture frequently have a poor dietary calcium intake and may have vitamin D deficiency, although histologically defined osteomalacia is uncommon [1]. Calcium and vitamin D deficiency contribute to the pathogenesis of hip fracture through an effect on bone mineral density, inducing osteoporosis by stimulating the increased production of parathyroid hormone (PTH). This secondary hyperparathyroidism is found in up to half of those admitted with hip fracture [2, 3].

Calcium and vitamin D supplementation has been shown to be effective in reducing secondary hyperparathyroidism [4, 5] and in reducing the incidence of hip and other non-vertebral fractures in elderly women [5, 6].

In selecting hip fracture patients who might be offered such supplementation as secondary fracture prevention, it is useful to characterize PTH, calcium and vitamin D status. However, the timing of PTH measurements may be important. It has been suggested that measurements performed in the first weeks after hip fracture are an unreliable indicator of pre-fracture metabolic status and that PTH may be transiently elevated as a consequence of the stress associated with the injury [3, 7].

In this project, we investigated how fracture and surgery at the hip affect PTH status. Since we could not know a patient's PTH status immediately before hip fracture, we were unable to measure the consequences of fracture directly. Instead we followed up patients undergoing elective hip surgery, to define the change in PTH levels before and after the acute stress of hip surgery. These patients and those presenting with hip fracture were also followed into the recovery period, when PTH results should have returned to the `unstressed' pre-fracture values.

Methods

Firstly, we studied a group of eight `fit' elderly [8] patients undergoing elective total hip replacement for osteoarthritis of the hip. Blood samples were taken on admission (day 1) to give baseline pre-operative status and were repeated 2 days and 1 week after operation (day 3 and 8). Finally, community follow-up allowed measurement of PTH in the recovery period, 2-6 months after surgery.

Secondly, we studied 12 patients presenting with hip fracture after a fall from standing height or less. PTH levels were measured within 24 h of admission (day 1) to define the stressed post-fracture state and repeated 2 days and 1 week later (days 3 and 8) to define the changes during the post-operative period. Again, community follow-up provided blood samples from the recovery period, 2-6 months after surgery. The operation performed was the insertion of AO screws, or of a Thompson hemiarthroplasty, depending on the type of fracture.

In both projects the blood samples were taken without prior fasting. Samples from all four different time-points were run in the same assay. Serum electrolytes, urea, creatinine, calcium and albumin were measured. Serum calcium was corrected for the albumin level. Plasma PTH was measured using a two-site assay for the intact molecule (Ciba-Corning Diagnostics, Halstead, UK) as described previously [9, 10], with a reference range of 0.9-5.4 pmol/l. The inter- and intra-assay variations at 2.9 pmol/l are 9% and 7.2% respectively, and at 39.2 pmol/l are 5.4% and 3.4% respectively [10]. In addition, samples taken on initial admission and during recovery were analysed to measure 25-hydroxyvitamin D (250HD) using a competitive protein binding assay (Medgenex, 6220 Floris, Belgium) with a reference range of 8-50 ng/ml [10, 11].

For one of the hip replacement patients PTH results were only available pre-operatively and at 2 days after surgery, but PTH data were complete for all other subjects. Data were analysed by ANOVA, using the ARCUS statistical package.

Results

The eight patients receiving total hip replacements were aged 70 [+ or -] 0.8 years (mean [+ or -] SE); five were women. All had normal corrected calcium and PTH on admission, although two (25%) had low 250HD levels. The mean corrected calcium, 250HD and PTH at the four time-points are shown in Table 1. ANOVA showed no significant change in any of these measurements during follow-up. PTH results appeared unaffected by hip surgery (Figure 1).

[FIGURE 1 ILLUSTRATION OMITTED]

Table 1. Corrected calcium, 25-hydroxyvitamin D (250HD) and parathyroid hormone (PTH) in elective hip replacement patients (mean [+ or -] SEM)

                        Corrected [Ca.sup.2+]
                        (mmol/l)
Normal values           2.2-2.6
Values in patients
  undergoing elective
  hip replacement
   Pre-operative        2.49 [+ or -] 0.03
   Day 3                2.45 [+ or -] 003
   Day 8                2.50 [+ or -] 0.06
   Recovery             2.47 [+ or -] 0.04

                        250HD
                        (ng/ml)
Normal values           8-50
Values in patients
  undergoing elective
  hip replacement
   Pre-operative        25.10 [+ or -] 7.99
   Day 3                -
   Day 8                -
   Recovery             26.74 [+ or -] 8.41

                        PTH
                        (pmol/l)
Normal values           0.9-5.4
Values in patients
  undergoing elective
  hip replacement
   Pre-operative        3.75 [+ or -] 0.39
   Day 3                3.58 [+ or -] 0.57
   Day 8                3.84 [+ or -] 0.58
Recovery                4.29 [+ or -] 0.62