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Risk of vertebral fractures in hypoparathyroidism

Formenti AM1Tecilazich F1Giubbini R2Giustina A3. Rev Endocr Metab Disord. 2019 Aug 30. doi: 10.1007/s11154-019-09507-x. [Epub ahead of print]

Abstract

Parathyroid hormone (PTH) exerts both anabolic and catabolic actions on bone,depending on the duration and periodicity of exposure. Hypoparathyroidism is defined by inadequate production of PTH in the presence oflow serum calcium. In hypoparathyroidism it has been reported an increase in corticaland trabecular bone mass, but it is still unknown if these quantitative variations maybe accompanied by qualitative ones and increased bone strength. Despite the extensive data available on the effects of hypoparathyroidism on bone, itseffect on the hard end point in this area which is the risk of fractures still remainsunresolved and highly debated. As a matter of fact no previous review has focused onthis relevant clinical topic. This review will deal with the various aspects of bone metabolism (turn-over,density, quality) in hypoparathyroidism, focusing on the few data available on therisk of fracture and in particular of morphometric vertebral fractures, the emerging way to assess actual skeletal fragility particularly in secondary forms of osteoporosis.

Implications of the current findings in clinical practice, open issues and perspectives Currently, there is not enough literature available on which any clinical recommendations can be based. In fact, studies so far are scanty and contradictory. The first contradiction concerns the apparently different behaviour of appendicular vs vertebral fractures in hypoparathyroidism. However, this is not surprising since this discrepancy is observed in other conditions of secondary osteoporosis in which altered bone quality is reported as in hypoparathyroidism and is due to the different metabolic activity of cortical vs trabecular bone. In several forms of secondary osteoporosis, such as acromegaly and glucocorticoid induced osteoporosis, vertebral fractures are observed even in subjects with normal BMD [45–47]. Moreover, endocrine conditions characterized by low bone turn-over as hypoparathyroidism, such as growth hormone deficiency (GHD), are at elevated risk of fracture [48]. Therefore, it can be hypothesized a parallel U-shape behavior of fracture risk between PTH and GH deficiency and excess (Fig. 1) [18, 49]. In fact, both in GHD and hypoparathyroidism bone metabolism is low and in hyperparathyroidism and acromegaly is high whereas all these conditions are (or may be) characterized by an increased risk of fracture. However, interestingly, although BMD is not a good predictor of bone fragility in secondary osteoporosis [50] it has to be noted that BMD findings are opposite in GHD (low-normal) [51] vs hypoparathyroidism (normal-high) [23] and in acromegaly (normal-high) [52] vs hyperparathyroidism (low-normal) [16, 17]. Mechanisms underlying these discrepancies still need to be elucidated. The second contradiction in the existing Literature concerns the prevalence and incidence of vertebral fractures in post-surgical hypoparathyroidism: only two very small and quite old studies have been published on the topic [28, 43]. One apparently suggesting hypoparathyroidism to be protective and on the contrary the other to be predisposing to an increased risk of morphometric fractures. In addition to the low number of subjects enrolled, which could have led to casual results due to selection bias, a possible explanation could be the negative influence of long standing menopause and history of the disease in the study with reported increased prevalence of fractures vs the negative one. Another area of uncertainty concerns the role of conventional treatment of hypoparathyroidism in the possibly increased risk of fracture (calcitriol could exert a negative effect on bone and high doses of cholecalciferol could have a paradox effect in inducing falls and the potential preventive role of PTH substitution on fracture risk) [22]. Therefore, based on available data, an active surveillance on skeletal events can be recommended in hypoparathyroidism, particularly in post-menopausal patients. Vertebral morphometry with DEXA currently appears the method of choice for this proactive evaluation due to patient convenience (this may be done contextually with BMD measurement) as well to greatly reduced radiation exposure of the patients. Large cross-sectional and prospective studies are needed to assess the real prevalence of morphometric vertebral fractures in post-surgical hypoparathyroidism. Longitudinal studies in idiopathic hypoparathyroidism are needed to assess risk factors and time of onset of these events. Finally, patients with prevalent vertebral fractures should be carefully evaluated for their treatment of hypoparathyroidism which, if not optimally controlling the patients should be considered for a switch to PTH replacement [22].