Absence of calcitriol causes increased lactational bone loss and lower milk calcium, but does not impair post-lactation recovery of bone mass, mineralization, or strength in <em>Cyp27b1</em> null mice — ASN Events
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  3. Absence of calcitriol causes increased lactational bone loss and lower milk calcium, but does not impair post-lactation recovery of bone mass, mineralization, or strength in Cyp27b1 null mice

Absence of calcitriol causes increased lactational bone loss and lower milk calcium, but does not impair post-lactation recovery of bone mass, mineralization, or strength in Cyp27b1 null mice (#39)

Brittany R Gillies 1 , Brittany A Ryan 1 , Brett A Tonkin 2 , Ingrid J Poulton 2 , Yue Ma 1 , Beth J Kirby 1 , Natalie A Sims 2 , René St-Arnaud 3 , Christopher S Kovacs 1
  1. Memorial University of Newfoundland, St. John's, NEWFOUNDLAND AND LABRADOR, Canada
  2. St. Vincent's Institute, University of Melbourne, Melbourne
  3. McGill University, Quebec, QC, Canada

We hypothesized that adaptation to the calcium supply demands of pregnancy and lactation do not require calcitriol. Adult Cyp27b1 nulls lack calcitriol and have hypocalcemia, hypophosphatemia, and rickets; a calcium, phosphorus and lactose-enriched “rescue” diet prevents these changes.

We studied sister WT and null pairs raised on the rescue diet from weaning.

Bone mineral content (DXA) increased >30% in pregnant nulls (0.42±0.03 to 0.56±0.03g), declined in lactation to 0.41±0.03g, and increased to 0.54±0.04g by 4 weeks post-weaning. WT showed less marked changes. MicroCT revealed that lactating WT and nulls lost trabecular bone. In lactating nulls, femoral cortical thickness declined >30% (183±6 to 131±6 mm) and endocortical perimeter increased (3.17±0.05 to 4.48±0.6); both recovered to baseline after weaning; there were no such changes in WT. Histomorphometry revealed a profound increase in osteoid surface in lactating nulls (62.7±5.8% vs. 0.29±0.29 in WT) which recovered after weaning to 10.0±3.1%. By 3-point bending test, nulls had a >50% decline in ultimate load to failure that recovered after weaning (1.80±0.09 g at baseline; 0.84±0.05 g at end-lactation, 1.67±0.06 g at 4 weeks post-weaning). At mid-lactation, milk calcium content was 30% lower in nulls (1.0±0.2 vs. 1.5±0.1 g/g in WT). Serum PTH was markedly elevated in nulls at baseline (2,815±1,292 vs. 8.4±3.9 ng/l in WT), reduced to 194±93 ng/ml in pregnancy, increased to 5,500±680 ng/ml in lactation, and remained high post-weaning.

Pregnant nulls gained BMC and had reduced secondary hyperparathyroidism, implying increased intestinal calcium delivery. Lactating nulls lost more bone mass and strength than WT, accompanied by increased osteoid, reduced milk calcium, and worsened secondary hyperparathyroidism. This implies suboptimal intestinal calcium absorption.  Post-weaning, bone mass, mineralization, and strength recovered fully.

In conclusion, calcitriol-independent mechanisms regulate calcium and trabecular bone metabolism during pregnancy and post-weaning but not during lactation; calcitriol may protect cortical bone during lactation.