Scalp cooling versus standard cold-cap in preventing chemotherapy-induced alopecia in patients with localized breast cancer: ICELAND protocol, a randomized controlled trial and economic evaluation.

Primary hyperparathyroidism (PHPT) is a relatively common medical condition around the world, being the most common etiology of hypercalcemia in the outpatient population []. Historically defined as hypercalcemia and elevated or non-suppressed parathyroid hormone (PTH) levels, it is nowadays accepted to diagnose PHPT in normocalcemic patients with elevated PTH levels and hypercalciuria [,]. Its age-adjusted prevalence in the healthy population of the United States of America has been estimated at 233 and 85 per 100,000 women and men, respectively []. In Canada, the prevalence of PHPT amongst community-dwelling adults is estimated at 3.3% and 1.4% (normocalcemic and classical forms, respectively) []. Incidence has remained relatively stable at 21.6 per 100,000 person-years in the last decades, after peaking at 82.5 per 100,000 person-years in the 1970s, most likely due to serum calcium being tested more frequently []. The consequences of PHPT are varied, ranging from hypercalciuria to nephrolithiasis, chronic kidney disease (CKD), constipation, osteoporosis, neuropsychiatric symptoms and bone/joint pain. Among these, depression and bone/joint pain may not be linked to the level of serum calcium but may still be relieved by definitive surgical cure [,]. It has even been suggested to screen every patient for occult urolithiasis given its high prevalence (21%) [,]. PHPT and its detrimental effects on bone health have long been known, particularly with respect to cortical bone such as the distal radius, hence the relatively high prevalence of osteoporosis in PHPT cohorts, with some estimates being as high as 48.4% [,]. Indeed, the Canadian Multicentre Osteoporosis Study (CaMoS) has shown that patients with PHPT have lower BMD values compared to healthy controls at the lumbar spine, femoral neck and total hip []. Historically linked to deficient sunlight exposure with a North-to-South gradient, vitamin D deficiency (VD) is common in Northern resource-rich countries. With better physician awareness in the last few years, vitamin D supplementation has been more widespread, with a decrease in VD prevalence and a reversal of the North-to-South gradient []. Population-wide surveys in Canada from 2016 to 2019 estimated that 6.8% of the population aged three to 79 years old has VD, while 19.3% of the population has levels meeting the insufficient range []. Purely by chance, one could expect these two conditions to be comorbid in any individual given their respective prevalence, but there seems to be an epidemiological link, for it has been reported that between 36.4 and 81% of patients with PHPT have VD [,]. Physiopathological interactions between vitamin D and PHPT have been demonstrated, a topic this review aims to further explore. First, we will begin by explaining the relevant physiology. Then, we will discuss whether it is prudent to replenish VD in patients with PHPT, given the available data on safety and possible benefits, with a specific emphasis on bone mineral density (BMD).