Calcium therapy for calcitriol-resistant rickets

Hochberg, Zèev; Tiosano, Dov; Even, Lea

doi:10.1016/s0022-3476(05)81919-5

Cited by 112 publications

(43 citation statements)

References 26 publications

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“…This conclusion is based on the observation that mineral and skeletal phenotypes of HVDRR patients are reversed when these patients are treated with intravenous or high oral calcium (191). In addition, when Vdr null mice (which represent an animal model of HVDRR) are fed a rescue diet high in calcium and lactose, rickets and osteomalacia are prevented (18,258,292), further indicating that impaired bone mineralization as a consequence of defective VDR signaling results from impaired intestinal calcium absorption.…”

Section: Overall Process Of Vitamin D-mediated Intestinal Calcium Absmentioning

confidence: 99%

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

1,358

1,234

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, [1,25(OH) 2 D 3 ] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH) 2 D 3 action involves the direct binding of the 1,25(OH) 2 D 3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH) 2 D 3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH) 2 D 3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

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Section: Overall Process Of Vitamin D-mediated Intestinal Calcium Absmentioning

confidence: 99%

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

1,358

1,234

View full text Add to dashboard Cite

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“…Repeated intravenous or intracaval calcium infusions, or high oral dose calcium, have been shown to normalize calcium, phosphorus, PTH, alkaline phosphatase; rickets was prevented or healed in these children (36,259,312,727). In one case series, the use of parenteral calcium caused growth velocity to increase, bone pain to decrease, and biochemical abnormalities to normalize within a year; it also enabled some affected children to walk for the first time ever (259). Rickets healed more rapidly in younger patients and when parenteral calcium was used instead of high dose oral calcium.…”

Section: Observational Studies and Case Reportsmentioning

confidence: 99%

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Kovacs

2014

Physiological Reviews

197

188

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Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24 -48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium.

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“…Similar to the VDR null mice, this treatment leads to correction of mineral and bone abnormalities but not to the restoration of hair growth. 39 Similarly, there is no effective treatment for hair regrowth in patients with APL. The parents of the patients with VDDR IIA in the present study were able to recognize the new patients in the family by the hair loss, which appears prior to the bony abnormalities.…”

Section: 23mentioning

confidence: 99%