Treatment of congenital osteopetrosis with high-dose calcitriol

L. Key, D. Carnes, S. Cole, M. Holtrop, Z. Bar-Shavit, F. Shapiro, R. Arceci, J. Steinberg, C. Gundberg, A. Kahn

Research output: Contribution to journalArticle

Abstract

We administered high doses of calcitriol (up to 32 μg per day) to an infant with malignant osteopetrosis, in an attempt to stimulate bone resorption. The patient was placed on a low-calcium diet to prevent hypercalcemia. Measures of bone turnover increased during calcitriol therapy; hydroxyproline excretion rose from 140 to 1358 μg per milligram of creatinine per 24 hours, with parallel increased in the ratio of calcium to creatinine in the urine, urinary gamma-carboxyglutamic acid, serum osteocalcin, and serum alkaline phosphatase. A pretreatment bone-biopsy specimen contained no osteoclasts with ruffled borders, a feature of active osteoclasts. After 11 days of calcitriol, ruffled borders were noted. After three months, numerous osteoclasts with ruffled borders and associated bony disruption were evident. Before therapy, the patient's monocytes were incapable of in vitro bone resorption, but after calcitriol, their resorptive capacity was increased to 3.3 times control levels. These data demonstrate that calcitriol increased bone mineral and matrix turnover in our patient. However, during the three months of calcitriol therapy there was only slight clinical improvement in her severe disease. Early and sustained treatment with calcitriol may be useful in osteopetrosis.

Original languageEnglish (US)
Pages (from-to)409-415
Number of pages7
JournalNew England Journal of Medicine
Volume310
Issue number7
StatePublished - 1984
Externally publishedYes

Fingerprint

Osteopetrosis
Calcitriol
Osteoclasts
Bone Resorption
Therapeutics
Creatinine
1-Carboxyglutamic Acid
Calcium
Bone Matrix
Bone Remodeling
Hydroxyproline
Osteocalcin
Hypercalcemia
Serum
Minerals
Alkaline Phosphatase
Monocytes
Urine
Diet
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Key, L., Carnes, D., Cole, S., Holtrop, M., Bar-Shavit, Z., Shapiro, F., ... Kahn, A. (1984). Treatment of congenital osteopetrosis with high-dose calcitriol. New England Journal of Medicine, 310(7), 409-415.

Treatment of congenital osteopetrosis with high-dose calcitriol. / Key, L.; Carnes, D.; Cole, S.; Holtrop, M.; Bar-Shavit, Z.; Shapiro, F.; Arceci, R.; Steinberg, J.; Gundberg, C.; Kahn, A.

In: New England Journal of Medicine, Vol. 310, No. 7, 1984, p. 409-415.

Research output: Contribution to journalArticle

Key, L, Carnes, D, Cole, S, Holtrop, M, Bar-Shavit, Z, Shapiro, F, Arceci, R, Steinberg, J, Gundberg, C & Kahn, A 1984, 'Treatment of congenital osteopetrosis with high-dose calcitriol', New England Journal of Medicine, vol. 310, no. 7, pp. 409-415.
Key L, Carnes D, Cole S, Holtrop M, Bar-Shavit Z, Shapiro F et al. Treatment of congenital osteopetrosis with high-dose calcitriol. New England Journal of Medicine. 1984;310(7):409-415.
Key, L. ; Carnes, D. ; Cole, S. ; Holtrop, M. ; Bar-Shavit, Z. ; Shapiro, F. ; Arceci, R. ; Steinberg, J. ; Gundberg, C. ; Kahn, A. / Treatment of congenital osteopetrosis with high-dose calcitriol. In: New England Journal of Medicine. 1984 ; Vol. 310, No. 7. pp. 409-415.
@article{edf94d4074b04544be1737f6b87c120a,
title = "Treatment of congenital osteopetrosis with high-dose calcitriol",
abstract = "We administered high doses of calcitriol (up to 32 μg per day) to an infant with malignant osteopetrosis, in an attempt to stimulate bone resorption. The patient was placed on a low-calcium diet to prevent hypercalcemia. Measures of bone turnover increased during calcitriol therapy; hydroxyproline excretion rose from 140 to 1358 μg per milligram of creatinine per 24 hours, with parallel increased in the ratio of calcium to creatinine in the urine, urinary gamma-carboxyglutamic acid, serum osteocalcin, and serum alkaline phosphatase. A pretreatment bone-biopsy specimen contained no osteoclasts with ruffled borders, a feature of active osteoclasts. After 11 days of calcitriol, ruffled borders were noted. After three months, numerous osteoclasts with ruffled borders and associated bony disruption were evident. Before therapy, the patient's monocytes were incapable of in vitro bone resorption, but after calcitriol, their resorptive capacity was increased to 3.3 times control levels. These data demonstrate that calcitriol increased bone mineral and matrix turnover in our patient. However, during the three months of calcitriol therapy there was only slight clinical improvement in her severe disease. Early and sustained treatment with calcitriol may be useful in osteopetrosis.",
author = "L. Key and D. Carnes and S. Cole and M. Holtrop and Z. Bar-Shavit and F. Shapiro and R. Arceci and J. Steinberg and C. Gundberg and A. Kahn",
year = "1984",
language = "English (US)",
volume = "310",
pages = "409--415",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "7",

}

TY - JOUR

T1 - Treatment of congenital osteopetrosis with high-dose calcitriol

AU - Key, L.

AU - Carnes, D.

AU - Cole, S.

AU - Holtrop, M.

AU - Bar-Shavit, Z.

AU - Shapiro, F.

AU - Arceci, R.

AU - Steinberg, J.

AU - Gundberg, C.

AU - Kahn, A.

PY - 1984

Y1 - 1984

N2 - We administered high doses of calcitriol (up to 32 μg per day) to an infant with malignant osteopetrosis, in an attempt to stimulate bone resorption. The patient was placed on a low-calcium diet to prevent hypercalcemia. Measures of bone turnover increased during calcitriol therapy; hydroxyproline excretion rose from 140 to 1358 μg per milligram of creatinine per 24 hours, with parallel increased in the ratio of calcium to creatinine in the urine, urinary gamma-carboxyglutamic acid, serum osteocalcin, and serum alkaline phosphatase. A pretreatment bone-biopsy specimen contained no osteoclasts with ruffled borders, a feature of active osteoclasts. After 11 days of calcitriol, ruffled borders were noted. After three months, numerous osteoclasts with ruffled borders and associated bony disruption were evident. Before therapy, the patient's monocytes were incapable of in vitro bone resorption, but after calcitriol, their resorptive capacity was increased to 3.3 times control levels. These data demonstrate that calcitriol increased bone mineral and matrix turnover in our patient. However, during the three months of calcitriol therapy there was only slight clinical improvement in her severe disease. Early and sustained treatment with calcitriol may be useful in osteopetrosis.

AB - We administered high doses of calcitriol (up to 32 μg per day) to an infant with malignant osteopetrosis, in an attempt to stimulate bone resorption. The patient was placed on a low-calcium diet to prevent hypercalcemia. Measures of bone turnover increased during calcitriol therapy; hydroxyproline excretion rose from 140 to 1358 μg per milligram of creatinine per 24 hours, with parallel increased in the ratio of calcium to creatinine in the urine, urinary gamma-carboxyglutamic acid, serum osteocalcin, and serum alkaline phosphatase. A pretreatment bone-biopsy specimen contained no osteoclasts with ruffled borders, a feature of active osteoclasts. After 11 days of calcitriol, ruffled borders were noted. After three months, numerous osteoclasts with ruffled borders and associated bony disruption were evident. Before therapy, the patient's monocytes were incapable of in vitro bone resorption, but after calcitriol, their resorptive capacity was increased to 3.3 times control levels. These data demonstrate that calcitriol increased bone mineral and matrix turnover in our patient. However, during the three months of calcitriol therapy there was only slight clinical improvement in her severe disease. Early and sustained treatment with calcitriol may be useful in osteopetrosis.

UR - http://www.scopus.com/inward/record.url?scp=0021350813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021350813&partnerID=8YFLogxK

M3 - Article

C2 - 6546410

AN - SCOPUS:0021350813

VL - 310

SP - 409

EP - 415

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 7

ER -