This is a phase IV, randomized, prospective open label study designed to evaluate the effect of two different amounts of vitamin D3 supplementation (daily 800 IU and daily 2000 IU) vs no supplementation on skeletal and non-skeletal manifestations of PHPT in postmenopausal women. Two groups of postmenopausal women with PHPT will be recruited: a) asymptomatic PHPT patients (subjects not fulfilling the surgical criteria); b) symptomatic PHPT patients (surgery group).
The primary endpoint is to evaluate the effect of normal and/or high vitamin D3 supplementation vs no supplementation on the skeletal complications of PHPT. Bone mineral density at the lumbar spine, hip and distal one-third radius will be assessed. The secondary endpoint is to evaluate the effect of the supplementation on other skeletal parameters (trabecular bone score, fractures); number of falls; creatinine clearance and urinary calcium excretion, lipid and glucose metabolism (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, RPC and total homocysteinemia, APO B, APO A; glucose-tolerance test in non-diabetic and serum glucose and insulin measured at baseline and at 120 minutes in diabetic patients; HOMA-IR index); cardiac and vascular involvement (diastolic dysfunction, left ventricular hypertrophy, cardiac calcium deposits in the myocardium, aortic and mitral valve calcification + carotid intima-media thickness + carotid plaque + percent of carotid stenosis). Postmenopausal women with PHPT aged 45-80 years will be studied.
The study will provide novel information on relevant clinical outcomes in patients with PHPT and the results will clarify whether vitamin D supplementation could influence the natural history of the disease and/or the recovery of the complications after surgery. Few and inconsistent data are available in PHPT in terms of reversibility of the non-classical complications after surgery and/or the possible role of vitamin D on these outcomes.
The study will provide novel information on relevant clinical outcomes in patients with PHPT and the results will clarify whether vitamin D supplementation could influence the natural history of the disease and/or the recovery of the complications after surgery. The effects of vitamin D on the non-skeletal complications, have not been well define so far nor in PHPT neither in the general, non-PHPT population. Additionally, few and inconsistent data are available in PHPT in terms of reversibility of the non-classical complications after surgery and/or the possible role of vitamin D on these outcomes.
The composite endpoints of the project will provide useful data in the definition of clinical indications for vitamin D supplementation and for surgery in PHPT. We will clarify the role of vitamin D supplementation of many complications of PHPT that currently represent criteria for surgery and on the non-classical complications that, even though not included among recommendations for parathyroidectomy, are mostly prevalent in PHPT patients. In PHPT patients not fulfilling surgical
criteria, a higher prevalence of fractures (OR= 3), all cause of mortality (Standardised mortality ratio = 2.62) and particularly cardiovascular-related mortality (Standardised mortality ratio = 2.68) have indeed been recently reported. Among the causes of cardiovascular disease, a derangement of lipids and glucose metabolism has been suggested.
The observed results could therefore lead to a revision of the current general guidelines, modifying the criteria that advise physicians for parathyroidectomy. We will also have data on how treatment with vitamin D could reduce the morbidity and mortality associated with PHPT and consequently the expenses for the National Healthcare System. The use of different doses of vitamin D will also be of help in defining specific clinical indications for supplementation in these patients.
Finally, results from the secondary endpoints will also provide useful details on the relationship between vitamin D metabolism and PHPT that are at the basis of the highly clinically evident prevalence of hypovitaminosis D in PHPT patients. Also, we will have novel data on the bioavailability and pharmacokinetics of vitamin D supplementation in these specific setting of patients. This could have an impact from a clinical point of view and be suitable for genetic and endocrine counselling.