Elsevier

Bone

Volume 35, Issue 1, July 2004, Pages 312-319
Bone

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis

https://doi.org/10.1016/j.bone.2004.02.003Get rights and content

Abstract

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD ≤ 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD ≤ 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD ≤ 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.

Introduction

The prevalence of ‘vitamin D insufficiency’ is well documented in the frail and institutionalized elderly but is becoming increasingly recognized among the healthy, community dwelling, elderly, and middle-aged subjects [1], [2], [3]. High prevalence rates have also been reported in patients with established osteoporosis presenting to secondary care [4], [5], [6]. Biochemically, the increase in PTH [7], [8], [9], [10] maintains calcium homeostasis but at the expense of increased bone turnover [11], significant bone loss, and increased risk of fracture [12], [13]. However, the threshold level of 25OHD defining ‘vitamin D insufficiency’ still remains unclear [14]. Peacock et al. [15] introduced the term ‘insufficiency’ for serum 25OHD concentrations between 25 and 50 nmol/l. A Dutch study found that 25OHD concentrations below 30 nmol/l resulted in secondary hyperparathyroidism and a decrease in bone mineral density (BMD) [16]. More recently, similar thresholds have been used by others [1], [2], [13]. However, because ‘vitamin D insufficiency’ is defined biochemically as the degree of hypovitaminosis D resulting in an increase in PTH secretion [17], it may be more appropriate to include a threshold level of PTH in the disease definition. The importance of this is justified further in that not all patients with hypovitaminosis D manifest the biochemical or bone histomorphometric effects of PTH excess whatever the threshold level of 25OHD [4], [18], [19], [20].

The aim of this study was to evaluate the effects of hypovitaminosis D (defined as a 25OHD ≤ 30 nmol/l) and a blunted PTH response (defined arbitrarily as a PTH within the hospital standard laboratory reference range) on calcium homeostasis, bone turnover, and BMD in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as PTH above the hospital standard laboratory reference range) and vitamin-replete subjects.

Section snippets

Subjects

Postmenopausal women aged ≥60 years with a vertebral fracture presenting to the Metabolic Bone Clinic, City Hospital, Nottingham, UK, over 24 months were evaluated. All subjects underwent a full physical examination, blood investigations, and bone densitometric and morphometric evaluation. Inclusion criteria included all patients with a t score ≤−2.5 (standard deviation (SD) units related to the young normal mean value) at either the spine or total hip sites or both (osteoporosis WHO

Patient characteristics

Baseline patient characteristics are presented in Table 1.

The age range of the subjects was 60–80 years. Five percent (21/421) had an early menopause, defined as occurring before the age of 45 years, and 4% (17/421) had a low body mass index (<20 kg/m2). There were seven patients of Indian and Pakistani origin, with the remainder being Caucasian. One-third of the patients had more than one vertebral fracture at presentation and 31% gave a history of previous nonspine fracture. The mean time

Discussion

This study confirms the high prevalence of hypovitaminosis D in postmenopausal women with established vertebral osteoporosis presenting to secondary care that is consistent with previous reports [4], [5], [6]. The inverse correlation between 25OHD and PTH has similarly been reported [4], [23] together with the strength of the relationship [1], [3] and seasonal variation [5], [6]. However, it was a surprise to find that secondary hyperparathyroidism (defined arbitrarily as a PTH above the

Acknowledgements

The authors are grateful to the research nurses in the Metabolic Unit for their help in collating the data. We are also grateful to Isabel Fowler in the Department of Clinical Chemistry for her support in preparing and analyzing some of the biochemical samples.

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    This work was supported by a Research and Development (R&D) grant, Nottingham City Hospital.

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