Clinical Endocrinology (2000) 52, 329±338 329 q 2000 Blackwell Science Ltd The effects of age and gender on parathyroid hormone dynamics Susan T. Haden, Edward M. Brown, Shelley Hurwitz, Jennifer Scott and Ghada El-Hajj Fuleihan Endocrine-Hypertension Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA (Received 13 July 1999; returned for revision 22 August 1999; ®nally revised 8 September 1999; accepted 7 October 1999) Summary BACKGROUND AND AIMS Hyperparathyroidism is a risk factor for bone loss. An age-related increase in parathyroid hormone (PTH) level has been demon- strated in several studies. It has been suggested that the type II osteoporotic syndrome, a condition of increased prevalence among elderly women, may be at least partially caused by elevations in intact parathyroid hormone (iPTH) levels. To date, however, the effects of age and gender per se on PTH dynamics in healthy subjects independent of other risk factors such as vitamin D de®ciency and/or impaired renal function that can impact on parathyroid function, remain unknown. In this study, we used citrate and calcium (Ca) infusions to characterize the impact of age and gender on PTH dynamics in normal subjects. SUBJECTS AND METHODS Twelve young women with mean age 6 SD of 26´4 6 1´6 years, 12 young men with mean age of 26´6 6 1´3 years, 12 older women with mean age of 68´6 6 1´3 years and 12 older men with mean age of 67´2 6 1´6 years were studied. The sigmoidal curves relating serum iPTH to serum levels of ionized Ca (Ca i ) were characterized by maxi- mal and minimal iPTH levels, the set-points (levels of Ca i causing half-maximal suppression of iPTH), and the slopes of the curves at the set-points. RESULTS Baseline serum Ca, Ca i , 25 hydroxyvita- min D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH) 2 D 3 ] levels, as well as the set-points, slopes and minimal values of the sigmoidal curves relating Ca i to iPTH, did not differ among the four groups. iPTH levels at baseline were slightly but not signi®cantly higher in the older age groups (P  0´18). The maximal iPTH level was 25% higher in the older women than in the younger women, although this difference was not signi®cant (P  0´29). However, the integrated iPTH responses calculated from the areas under the curves (AUC) of iPTH levels vs. time during the calcium and citrate infusions were signi®cantly higher in postmenopausal women than in young women during both infusions and in older men than in young men during the calcium infusion. There was no effect of gender on serum iPTH levels. CONCLUSIONS In both women and men, ageing per se, independent of changes in vitamin D economy or renal function, is associated with an increase in inte- grated PTH secretory response to changes in serum calcium. No alterations in the Ca i /iPTH set-point were present. The biological relevance of these modest increments in integrated iPTH levels during dynamic testing in older healthy men and women remain uncertain. Maximal bone mass is achieved between 20 and 40 years of age, after which bone loss occurs in both genders. Over a lifetime, women lose 50% of their trabecular bone mass and 30% of their cortical bone mass, whereas men lose two-thirds of these amounts (Riggs et al., 1981; Mazess, 1990; Riggs & Melton, 1992). Bone loss with ageing is the result of complex interactions of multiple factors, including genetic traits, environmental variables, diet, physical activity, gonadal status and calciotropic hormones (Sherman et al., 1990; Silverberg et al., 1989; Hernandez-Avila et al., 1991; Cauley et al., 1995; Cummings et al., 1995; Silverberg et al., 1995). Because of the signi®cant impact of parathyroid hormone (iPTH) on calcium (Ca) and skeletal homeostasis, investigators have evaluated serum iPTH levels in elderly subjects and have demonstrated signi®cant increments with age (Kotowicz et al., 1990; Orwoll & Meier, 1986; Sherman et al., 1992; Prince et al., 1995; Khosla et al., 1997). These increments in baseline serum iPTH levels may play an important role in age-related bone loss (Orwoll & Meier, 1986; Sherman et al., 1992). Indeed, several studies have shown an inverse relationship between iPTH levels and bone mass at several skeletal sites (Orwoll & Meier, 1986; Benhamou et al., 1991; Villareal et al., 1991; Sherman et al., 1992). Likewise, even mild primary hyperparathy- roidism is usually accompanied by some bone loss, particularly cortical bone (Silverberg et al., 1989). Correspondence: Ghada El-Hajj Fuleihan, Endocrine Division, American University of Beirut Medical Center, Bliss Street, Beirut, Lebanon. Fax: 11 961 1 744464; E-mail: address: gf01@aub.edu.lb