Pamidronate preserves bone mass for at least 2 years following acute administration for pediatric burn injury

Przkora, René; Herndon, David N.; Sherrard, Donald J.; Chinkes, David L.; Klein, Gordon L.

doi:10.1016/j.bone.2007.04.195

Cited by 55 publications

(32 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oxandrolone is the most studied anabolic drug in burn patients, is safe and has demonstrated beneficial effects in lean mass restoration [39,40]. Antiresorptive agents such as bisphosphonates have been studied in burn children with promising result both on bone [41,42] and muscle mass [43]. Place of bone anabolic drugs (such as strontium ralenate or anti-sclerostin antibody) has to be specified in burn related bone loss management.…”

Section: Normal Rangesmentioning

confidence: 98%

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: A one-year pilot randomized controlled trial in adults with severe burns

Rousseau

Foidart-Desalle

Ledoux

et al. 2015

Burns

View full text Add to dashboard Cite

Section: Normal Rangesmentioning

confidence: 98%

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: A one-year pilot randomized controlled trial in adults with severe burns

Rousseau

Foidart-Desalle

Ledoux

et al. 2015

Burns

View full text Add to dashboard Cite

“…These early resorptive changes would explain the efficacy of acute intravenous administration of bisphosphonates in prevention of bone loss in children following burn injury [2, 5]. In addition, a study in adults within the first week following burns by Leblebici et al [9] demonstrated an elevation of urinary deoxypyridinoline excretion, also consistent with early increased resorption.…”

Section: Discussionmentioning

confidence: 99%

“…By 2 weeks post-burn patients already have adynamic bone as evidenced by markedly reduced bone formation [3–5], reduced urinary markers of bone resorption [4], and reduced osteoblast differentiation [6]. However, if bisphosphonates are given intravenously within the first 10 days of the burn injury, the bone loss is entirely blocked [2, 5]. Therefore, it is possible that the acute bone loss could be the result of bone resorption.…”

Section: Introductionmentioning

confidence: 99%

Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study

et al. 2013

Self Cite

View full text Add to dashboard Cite

Treatment with bisphosphonates within the first 10 days of severe burn injury completely prevents bone loss. We therefore postulated that bone resorption occurs early post burn and is the primary explanation for acute bone loss in these patients. Our objective was to assess bone for histological and biomechanical evidence of early resorption post burn. We designed a randomized controlled study utilizing a sheep model of burn injury. Three sheep received a 40 % total body surface area burn under isoflurane anesthesia, and three other sheep received cotton-smoke inhalation and served as control. Burned sheep were killed 5 days post procedure and controls were killed 2 days post procedure. Backscatter scanning electron microscopy was performed on iliac crests obtained immediately postmortem along with quantitative histomorphometry and compression testing to determine bone strength (Young’s modulus). Blood ionized Ca was also determined in the first 24 h post procedure as was urinary CTx. Three of three sheep killed at 5 days had evidence of scalloping of the bone surface, an effect of bone resorption, whereas none of the three sheep killed at 2 days post procedure had scalloping. One of the three burned sheep killed at 5 days showed quantitative doubling of the eroded surface and halving of the bone volume compared to sham controls. Mean values of Young’s modulus were approximately one third lower in the burned sheep killed at 5 days compared to controls, p = 0.08 by unpaired t test, suggesting weaker bone. These data suggest early post-burn bone resorption. Urine CTx normalized to creatinine did not differ between groups at 24 h post procedure because the large amounts of fluids received by the burned sheep may have diluted urine creatinine and CTx and because the urine volume produced by the burned sheep was threefold that of the controls. We calculated 24 h urinary CTx excretion, and with this calculation CTx excretion/24 h in the burned sheep was nearly twice that of the controls. Moreover, whole blood ionized Ca measured at 3- to 6-h intervals over the first 24 h in both burn and control sheep showed a 6 % reduction versus baseline in the burned sheep with <1 % reduction in the control animals. This sheep model was previously used to demonstrate upregulation of the parathyroid calcium-sensing receptor within the timeframe of the present study. Because both early bone resorption, supported by this study, and calcium-sensing receptor upregulation, consistent with the observed reduction in blood ionized Ca, are mediated by proinflammatory cytokines that are present as part of the post-burn systemic inflammatory response, we may postulate that post-burn upregulation of the parathyroid calcium-sensing receptor may be an adaptive response to clear the blood of excess calcium liberated by cytokine-mediated bone resorption.

show abstract

“…By two weeks after the burn injury in children there are virtually no surface osteoblasts seen on iliac crest bone biopsy [3,7]. Study of glucocorticoid receptor messenger RNA (mRNA) in bone tissue by real time polymerase chain reaction (RTPCR) showed a trend toward reduction of the glucocorticoid receptor mRNA and a significant reduction of type I collagen mRNA in iliac crest bone biopsies of burned patients compared to controls [4].…”

Section: Overview Of Pertinent Pathophysiologic Responses To Burnsmentioning

confidence: 97%

“…Having provided evidence for progressive vitamin D deficiency following burn injury, we must place this in the context of resolving bone problems by one year post-burn, including the resumption of bone remodeling [7] and the resolution of hypocalcemia and hypoparathyroidism. Thus the progressive vitamin D deficiency post-burn may be responsible for failure of bone mass to return to a more normal range [24].…”

Section: The Natural History Of Vitamin D Me-tabolism Post-burnmentioning

confidence: 98%

The Interaction Between Burn Injury and Vitamin D Metabolism and Consequences for the Patient

Klein¹

2008

CCP

View full text Add to dashboard Cite

The stress and inflammatory responses to burn injury are associated with bone loss. The stress response entails production of large amounts of endogenous glucocorticoids that decrease osteoblasts on the mineralization surface of bone and decreases differentiation of marrow stromal cells into osteoblasts, thereby decreasing the amount of bone formation. Deficiency of osteoblasts also blocks osteoclastogenesis thus leading to low bone turnover and bone loss. The inflammatory response generates cytokines such as interleukin 1-beta and interleukin-6, which normally increase osteoclastogenic bone resorption via stimulation of osteoblast production of RANK ligand. However, in the absence of osteoblasts as a target we postulate that they attack the parathyroid gland chief cells and up-regulate the calcium-sensing receptor. The consequence of this upregulation is the lowering of the circulating calcium necessary to suppress parathyroid hormone production and the development of hypocalcemia and urinary calcium wasting. It is the parathyroid hormone suppression that causes us to postulate acute deficiency of 1,25-dihydroxyvitamin D and the consequence of this for post-burn metabolism could include derepression of the gene that controls renin production, leading to elevated levels of angiotensin II, which can contribute to insulin resistance, as can vitamin D deficiency itself. Moreover, the skin from burned patients cannot synthesize vitamin D normally. Thus vitamin D supplementation is the only means by which to ensure vitamin D sufficiency for burn victims. The proper requirement for vitamin D in acutely burned patients remains unknown.

show abstract

Pamidronate preserves bone mass for at least 2 years following acute administration for pediatric burn injury

Cited by 55 publications

References 18 publications

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: A one-year pilot randomized controlled trial in adults with severe burns

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: A one-year pilot randomized controlled trial in adults with severe burns

Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study

The Interaction Between Burn Injury and Vitamin D Metabolism and Consequences for the Patient

Contact Info

Product

Resources

About