The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review

Abstract

Summary Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, increases fracture risk. Primary osteoporosis is usually a result of reduced bone mineral density as a consequence of natural aging. Secondary osteoporosis is usually a result of a disease, such as cystic fibrosis, or medical treatment, such as corticosteroids or cancer treatment. Introduction Currently, ten million Americans are osteoporotic and an additional 34 million have the precursor condition, osteopenia. Osteoporosis leads to 1.5 million fractures and 500,000 hospitalizations annually. Osteoporosis-related fractures increase mortality and reduce quality of life. Calcitriol, the active form of vitamin D, regulates intestinal calcium absorption, among other actions. During the past four decades, many clinical trials investigating the effect of calcitriol on bone loss have been performed. Methods We conducted a systematic qualitative review of clinical trials that assessed calcitriol for the treatment of osteoporosis and bone loss. In these clinical trials, calcitriol was used as a monotherapy and in combination with other therapeutic bone agents. Results and conclusion Studies using calcitriol monotherapy, although not conclusive, found that calcitriol slowed the rate of bone loss in a variety of populations. Calcitriol in combination with other therapeutic bone agents was shown to have additional bone-preserving effects when compared to the use of therapeutic bone agents alone. A common side-effect of calcitriol therapy was hypercalcemia and hypercalciuria, but the degree of hypercalcemia was mild. Recent research found that intermittent dosing can reduce hypercalcemia rates. Calcitriol, alone or in combination with other agents, should be considered for the therapy of osteoporosis.

The clinical use of vitamin D metabolites and their potential developments: a position statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF)

“…As reported in a systematic review, calcitriol has been proven to be effective in decreasing or even reversing the rate of bone loss in a variety of vulnerable populations in trials lasting up to 8 years, especially when administered together with bone antiresorptive agents [63]. As expected, the prolonged use of calcitriol yields the common side effects of hypercalciuria and mild hypercalcemia, usually in the mild range, without any report of deaths or lifethreatening hypercalcemic episodes.…”

“…While 25-monohydroxylated vitamin D (calcidiol) may be used to optimize vitamin D status especially when the activity of hepatic hydroxylases is diminished [62], 1a-hydroxylated vitamin D analogs can be employed when renal hydroxylation is impaired, such as in the case of kidney failure or hypoparathyroidism, in order to favor calcium absorption and/or overcome the age-related decreased VDR expression [60,61,63].…”

“…These compounds have also been employed in diseases such as osteomalacia and osteoporosis in order to correct calcium malabsorption and/or overcome resistance to 1,25(OH) 2 D due to age-related decline in the expression of the VDR, thus ameliorating mineral and skeletal homeostasis, especially in postmenopausal women. In addition, they may display direct protective effects in bone and skeletal muscle through binding the VDR, increasing the BMD and muscle performance, thus decreasing the incidence of falls and fractures [63]. Active vitamin D metabolites are also called D-hormones since their effects occur independently of an effect on vitamin D status.…”

“…Since menopause itself is accompanied by a decrease in calcium absorption per se, mainly because of a resistance to calcitriol and a decrease of calcitriol levels, calcitriol has been employed in several studies in order to optimize mineral and skeletal homeostasis and decrease fracture rate in women with postmenopausal osteoporosis, as a monotherapy or in combination with other antifracture agents [59] (reviewed in [63] ). In these trials, calcitriol was administered daily, at a dose ranging from 0.25 to 1 mcg/day, with the majority of studies employing 0.5 mcg/day.…”

The Connotation of Kidney Stores Essence Theory and Kidney Endocrine Substance

“…α-Klotho also regulates the expression of vitamin D receptor [42]. It is clear that the lack of 1,25-dihydroxyvitamin D 3 can lead to osteoporosis [43]. Studies have shown that the introduction of variant KL-VS of the human KLOTHO gene in mice enhances cognitive function and increases serum α-klotho levels [44].…”