Endocrine DOI 10.1007/s12020-015-0582-1
LETTER TO THE EDITOR
Bone mineral content in growth hormone deficient children treated with growth hormone after withdrawal of supplementation with calcium, vitamin D and zinc Veena Ekbote1 • Anuradha Khadilkar1 • Zulf Mughal2
Received: 4 March 2015 / Accepted: 14 March 2015 Ó Springer Science+Business Media New York 2015
We have previously studied the effect of calcium, vitamin D and zinc supplementation on bone mass accrual of Indian growth hormone (GH) deficient children, while they were on GH therapy [1]. In addition to regular GH therapy (20 mg/m2/week), all children received vitamin D3 60,000 IU once in 3 months. Children from Group A (n = 15) were supplemented with calcium (calcium carbonate 500 mg/day) and children from Group B (n = 16) were supplemented with calcium (calcium carbonate 500 mg/day) and zinc (as per Indian recommendations: average 8 mg/day). The supplementation was carried out for a year. We found that bone mineral content improved with calcium and vitamin D supplementation as against GH therapy alone. With addition of zinc supplementation to calcium and vitamin D (Group B), the gain in bone mineral content was further enhanced. Prodam et al. (2013) have suggested a need for a longitudinal study to assess the effect of nutritional supplementation on the bone parameters in GH-treated GHD children [2]. In this letter, we report the findings of the follow-up of these children 1-year post-supplementation. At the end of 1 year of supplementation, all children were continued on GH therapy; however, neither group received calcium, vitamin D, or zinc. These children were then followed up after 1 year of withdrawal of supplementation. Height was measured and converted to Z-scores (HAZ) and an assessment of Tanner stage was carried out & Anuradha Khadilkar [email protected] 1
Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, India
2
Royal Manchester Children’s Hospital, Manchester M13 9WL, UK
as per standard protocol by a trained paediatric endocrinologist. Children’s total body less head bone mineral content (TB BMC) was assessed by dual energy X-ray absorptiometry (DXA) (GE, Lunar DPX Pro). At the end of a year of supplementation (i.e. at the beginning of the follow-up study), mean age of children was 10.4 ± 3 years and the HAZ were similar (p [ 0.1) between the two groups with a mean of -3.4 ± 1.3; similarly, there were no differences in the HAZ at 1 year after withdrawal of the supplementation between the groups (HAZ -2.9 ± 1.2). Furthermore, in the 1-year post-supplementation, 40 and 36 % children from group A and B, respectively, had entered puberty. As height strongly correlates with BMC, percent change in height adjusted BMC was assessed. It was found that, after the withdrawal of supplementation, the percent gain in height adjusted BMC was similar in both groups (22 %, p [ 0.1) (Fig. 1). Our pilot trial had shown that supplementation with calcium and vitamin D along with GH therapy in GHD Indian children had the potential for increasing bone mass accrual; this effect was further enhanced through the addition of zinc supplement. However, follow-up of these children 1-year post-supplementation (GH therapy was continued) showed that the effect of short-term supplementation with Ca, vitamin D and Zn on bone mass accrual in GH-treated GHD children may not continue after the withdrawal of supplementation. Zn is an essential component of the calcified matrix and is believed to have a potent stimulatory effect on osteoblastic bone formation. A direct effect of Zn on endochondral bone formation has also been reported in rats [1]. However, few studies report effect of zinc supplementation or withdrawal of supplement on bone mass. In an 18-month follow-up study (after 18 months calcium supplementation with 300 mg of elemental
123
Endocrine
post-supplementation with zinc is not known, supplementation with zinc especially in the presence of zinc deficiency has been found to increase bone mass. For a continued increase on bone mass, it is possible that a longer period of supplementation may be required. The study was approved by the ethics committee of the Hirabai Cowasji Jehangir Medical Research Institute, Pune, India. A written informed consent and an assent were obtained from parents and children before commencement of the study.
Conflict of interest
Fig. 1 Percentage gain in height adjusted bone mineral content in both groups post-supplementation and 1 year after withdrawal of supplementation
calcium), Lee et al. found that the increased gain in bone mass after calcium supplementation was reversible [3]. It has been suggested that the mechanism for increase in BMC by calcium supplementation is through the reduction in bone turnover markers; this effect no longer persists after the withdrawal of the supplement. Calcium supplementation is believed to decrease the remodelling of bone by suppressing PTH secretion, and the increase in BMD is a consequence of the filling of the remodelling space [4]. Although the exact mechanism of increase in bone mass
123
The authors declare no conflict of interest.
References 1. V. Ekbote, A. Khadilkar, S. Chiplonkar, Z. Mughal, V. Khadilkar, Enhanced effect of zinc and calcium supplementation on bone status in growth hormone-deficient children treated with growth hormone: a pilot randomized controlled trial. Endocrine 43, 686–695 (2013) 2. F. Prodam, G. Aimaretti, Could zinc supplementation improve bone status in growth hormone (GH) deficient children? Endocrine 43, 467–468 (2013) 3. W.T. Lee, S.S. Leung, D.M. Leung, J.C. Cheng, A follow-up study on the effects of calcium-supplement withdrawal and puberty on bone acquisition of children. Am. J. Clin. Nutr. 64, 71–77 (1996) 4. H.L. Lambert, R. Eastell, K. Karnik, J.M. Russell, M.E. Barker, Calcium supplementation and bone mineral accretion in adolescent girls: an 18-mo randomized controlled trial with 2-y follow-up. Am. J. Clin. Nutr. 87, 455–462 (2008)
LETTER TO THE EDITOR
Bone mineral content in growth hormone deficient children treated with growth hormone after withdrawal of supplementation with calcium, vitamin D and zinc Veena Ekbote1 • Anuradha Khadilkar1 • Zulf Mughal2
Received: 4 March 2015 / Accepted: 14 March 2015 Ó Springer Science+Business Media New York 2015
We have previously studied the effect of calcium, vitamin D and zinc supplementation on bone mass accrual of Indian growth hormone (GH) deficient children, while they were on GH therapy [1]. In addition to regular GH therapy (20 mg/m2/week), all children received vitamin D3 60,000 IU once in 3 months. Children from Group A (n = 15) were supplemented with calcium (calcium carbonate 500 mg/day) and children from Group B (n = 16) were supplemented with calcium (calcium carbonate 500 mg/day) and zinc (as per Indian recommendations: average 8 mg/day). The supplementation was carried out for a year. We found that bone mineral content improved with calcium and vitamin D supplementation as against GH therapy alone. With addition of zinc supplementation to calcium and vitamin D (Group B), the gain in bone mineral content was further enhanced. Prodam et al. (2013) have suggested a need for a longitudinal study to assess the effect of nutritional supplementation on the bone parameters in GH-treated GHD children [2]. In this letter, we report the findings of the follow-up of these children 1-year post-supplementation. At the end of 1 year of supplementation, all children were continued on GH therapy; however, neither group received calcium, vitamin D, or zinc. These children were then followed up after 1 year of withdrawal of supplementation. Height was measured and converted to Z-scores (HAZ) and an assessment of Tanner stage was carried out & Anuradha Khadilkar [email protected] 1
Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, India
2
Royal Manchester Children’s Hospital, Manchester M13 9WL, UK
as per standard protocol by a trained paediatric endocrinologist. Children’s total body less head bone mineral content (TB BMC) was assessed by dual energy X-ray absorptiometry (DXA) (GE, Lunar DPX Pro). At the end of a year of supplementation (i.e. at the beginning of the follow-up study), mean age of children was 10.4 ± 3 years and the HAZ were similar (p [ 0.1) between the two groups with a mean of -3.4 ± 1.3; similarly, there were no differences in the HAZ at 1 year after withdrawal of the supplementation between the groups (HAZ -2.9 ± 1.2). Furthermore, in the 1-year post-supplementation, 40 and 36 % children from group A and B, respectively, had entered puberty. As height strongly correlates with BMC, percent change in height adjusted BMC was assessed. It was found that, after the withdrawal of supplementation, the percent gain in height adjusted BMC was similar in both groups (22 %, p [ 0.1) (Fig. 1). Our pilot trial had shown that supplementation with calcium and vitamin D along with GH therapy in GHD Indian children had the potential for increasing bone mass accrual; this effect was further enhanced through the addition of zinc supplement. However, follow-up of these children 1-year post-supplementation (GH therapy was continued) showed that the effect of short-term supplementation with Ca, vitamin D and Zn on bone mass accrual in GH-treated GHD children may not continue after the withdrawal of supplementation. Zn is an essential component of the calcified matrix and is believed to have a potent stimulatory effect on osteoblastic bone formation. A direct effect of Zn on endochondral bone formation has also been reported in rats [1]. However, few studies report effect of zinc supplementation or withdrawal of supplement on bone mass. In an 18-month follow-up study (after 18 months calcium supplementation with 300 mg of elemental
123
Endocrine
post-supplementation with zinc is not known, supplementation with zinc especially in the presence of zinc deficiency has been found to increase bone mass. For a continued increase on bone mass, it is possible that a longer period of supplementation may be required. The study was approved by the ethics committee of the Hirabai Cowasji Jehangir Medical Research Institute, Pune, India. A written informed consent and an assent were obtained from parents and children before commencement of the study.
Conflict of interest
Fig. 1 Percentage gain in height adjusted bone mineral content in both groups post-supplementation and 1 year after withdrawal of supplementation
calcium), Lee et al. found that the increased gain in bone mass after calcium supplementation was reversible [3]. It has been suggested that the mechanism for increase in BMC by calcium supplementation is through the reduction in bone turnover markers; this effect no longer persists after the withdrawal of the supplement. Calcium supplementation is believed to decrease the remodelling of bone by suppressing PTH secretion, and the increase in BMD is a consequence of the filling of the remodelling space [4]. Although the exact mechanism of increase in bone mass
123
The authors declare no conflict of interest.
References 1. V. Ekbote, A. Khadilkar, S. Chiplonkar, Z. Mughal, V. Khadilkar, Enhanced effect of zinc and calcium supplementation on bone status in growth hormone-deficient children treated with growth hormone: a pilot randomized controlled trial. Endocrine 43, 686–695 (2013) 2. F. Prodam, G. Aimaretti, Could zinc supplementation improve bone status in growth hormone (GH) deficient children? Endocrine 43, 467–468 (2013) 3. W.T. Lee, S.S. Leung, D.M. Leung, J.C. Cheng, A follow-up study on the effects of calcium-supplement withdrawal and puberty on bone acquisition of children. Am. J. Clin. Nutr. 64, 71–77 (1996) 4. H.L. Lambert, R. Eastell, K. Karnik, J.M. Russell, M.E. Barker, Calcium supplementation and bone mineral accretion in adolescent girls: an 18-mo randomized controlled trial with 2-y follow-up. Am. J. Clin. Nutr. 87, 455–462 (2008)
