Medication

Medication Summary

Therapy includes antiresorptive agents such as bisphosphonates (eg, alendronate, risedronate, pamidronate, zoledronic acid) as well as calcium and vitamin D supplementation. Hormone replacement therapy (eg, estrogen, estrogen analogs) does not have a role in pediatric therapy unless the low bone mass is attributable to hypogonadism.

Preferred treatment of vitamin D deficiency is listed in the table below^[11]:

Table 5. Treatment of Vitamin D Deficiency (Open Table in a new window)

Age	Preparation and Dose^a
Infants, 0-12 mo	Vitamin D₂ or D₃ 50,000 IU weekly for 6 wk	or	Vitamin D₂ or D₃ 2000 IU daily for 6 wk
Infants, 0-12 mo	Followed by a maintenance dose of 400-1000 IU daily		Followed by a maintenance dose of 400-1000 IU daily
Children and adolescents, 1-18y	Vitamin D₂ or D₃ 50 000 IU weekly for 6-8 wk	or	Vitamin D₂ or D₃ 2000 IU daily for 6-8 wk
Children and adolescents, 1-18y	Followed by a maintenance dose of 600-1000 IU daily		Followed by a maintenance dose of 600-1000 IU daily

Vitamin D₂, ergocalciferol; vitamin D₃, cholecalciferol.

↵^a Vitamin D₃ may be more potent than vitamin D₂.

Table from: Golden NH, Abrams SA, Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics. 2014 Oct. 134 (4):e1229-43.

Class Summary

These agents decrease bone resorption and prevent bone loss from diminishing bone mass on an ongoing basis. They are available in parenteral and oral dosage forms for acute and chronic treatment, respectively.

Pamidronate (Aredia)

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Pamidronate inhibits both normal and abnormal bone resorption. It appears to inhibit bone resorption without as much impact on bone formation and mineralization. It is administered intravenously (IV), using a variety of regimens. Pamidronate is approved for use in hypercalcemia of malignancy and Paget disease. It has also been used in children with osteopenic bone disease.

Alendronate (Fosamax)

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Alendronate is an orally administered bisphosphonate that is approved as an antiresorptive agent to treat Paget disease and postmenopausal osteoporosis. Although a large trial of low dose alendronate did not show benefits for children with OI, the studies with higher doses have showed greater efficacy.

Risedronate (Actonel)

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Risedronate is an aminobisphosphonate. It inhibits bone resorption via actions on osteoclasts or osteoclast precursors. It is indicated for the prevention and treatment of osteoporosis. It has been demonstrated to have efficacy in children with mild/moderate OI.

Calcium

For optimal bone health, dietary sources of required daily calcium should be recommended in preference to calcium supplements, not only because of the improved bioavailability of dietary sources of calcium, but also to encourage lifelong healthy dietary habits for children and adolescents. The most commonly consumed dietary sources of calcium are milk, other dairy-containing products, and calcium-fortified juices. Oral calcium either as dietary intake or supplement should be routinely used in conjunction with vitamin D in the treatment of Vitamin D deficiency regardless of age or weight. The dose of a supplement can be selected based primarily on the content of elemental calcium. The most widely available calcium supplements are calcium carbonate and calcium citrate.

Vitamin D

Although routine 25OHD screening is not recommended for healthy children, children at risk of osteoporosis or vitamin D deficiency (with factors/conditions that reduce vitamin D synthesis or intake) should have their vitamin D status ascertained by measurement of a serum 25OHD concentration. Deficiency is defined as a concentration < 30 nmol/L and insufficiency a concentration 30–50 nmol/L, Deficiency, <30 nmol/L).

For treatment of nutritional rickets per the most recent Global Consensus Recommendations, the minimal recommended dose of vitamin D is 2000 IU/d (50 μg) for a minimum of 3 months. Oral treatment is preferred to intramuscular therapy. For daily treatment, both D2 and D3 are equally effective. When single large doses are used, D3 appears to be preferable compared to D2 because the former has a longer half-life. Vitamin D treatment is recommended for a minimum of 12 weeks, recognizing that some children may require longer treatment duration.

International Society for Clinical Densitometry. Official Positions of the International Society for Clinical Densitometry: Skeletal Health Assessment in Children From Infancy to Adolescence. 2019 ISCD Official Positions - Pediatric. Available at https://www.iscd.org/official-positions/2019-iscd-official-positions-pediatric/. 2019 May 28; Accessed: May 17, 2020.
Bachrach LK, Gordon CM, Section on Endocrinology. Bone densitometry in children and adolescents. Pediatrics. 2016 Oct. 138 (4):[QxMD MEDLINE Link]. [Full Text].
NIH. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000 Mar 27-29. 17(1):1-45. [QxMD MEDLINE Link].
Baim S, Leonard MB, Bianchi ML, et al. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom. 2008 Jan-Mar. 11(1):6-21. [QxMD MEDLINE Link].
Gordon CM, Leonard MB, Zemel BS, International Society for Clinical Densitometry. 2013 Pediatric Position Development Conference: executive summary and reflections. J Clin Densitom. 2014 Apr-Jun. 17 (2):219-24. [QxMD MEDLINE Link].
Zemel BS, Kalkwarf HJ, Gilsanz V, et al. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. 2011 Oct. 96 (10):3160-9. [QxMD MEDLINE Link].
Naylor KE, Eastell R, Shattuck KE, Alfrey AC, Klein GL. Bone turnover in preterm infants. Pediatr Res. 1999 Mar. 45(3):363-6. [QxMD MEDLINE Link].
Johnston CC Jr, Miller JZ, Slemenda CW, et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med. 1992 Jul 9. 327(2):82-7. [QxMD MEDLINE Link].
Lappe JM, Watson P, Gilsanz V, et al. The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. J Bone Miner Res. 2015 Jan. 30 (1):156-64. [QxMD MEDLINE Link].
Saraff V, Högler W. Endocrinology and adolescence: osteoporosis in children: diagnosis and management. Eur J Endocrinol. 2015 Dec. 173 (6):R185-97. [QxMD MEDLINE Link].
Golden NH, Abrams SA, Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics. 2014 Oct. 134 (4):e1229-43. [QxMD MEDLINE Link].
Ma NS, Gordon CM. Pediatric osteoporosis: where are we now?. J Pediatr. 2012 Dec. 161 (6):983-90. [QxMD MEDLINE Link].
Rauch F, Travers R, Parfitt AM, Glorieux FH. Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone. 2000 Jun. 26 (6):581-9. [QxMD MEDLINE Link].
Venturi G, Tedeschi E, Mottes M, et al. Osteogenesis imperfecta: clinical, biochemical and molecular findings. Clin Genet. 2006 Aug. 70 (2):131-9. [QxMD MEDLINE Link].
Lorenc RS. Idiopathic juvenile osteoporosis. Calcif Tissue Int. 2002 May. 70 (5):395-7. [QxMD MEDLINE Link].
Kelly HW, Van Natta ML, Covar RA, Tonascia J, Green RP, Strunk RC. Effect of long-term corticosteroid use on bone mineral density in children: a prospective longitudinal assessment in the childhood Asthma Management Program (CAMP) study. Pediatrics. 2008 Jul. 122(1):e53-61. [QxMD MEDLINE Link]. [Full Text].
Fuhlbrigge AL, Kelly HW. Inhaled corticosteroids in children: effects on bone mineral density and growth. Lancet Respir Med. 2014 Jun. 2 (6):487-96. [QxMD MEDLINE Link].
Halton J, Gaboury I, Grant R, et al. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res. 2009 Jul. 24 (7):1326-34. [QxMD MEDLINE Link].
Huber AM, Gaboury I, Cabral DA, et al. Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res (Hoboken). 2010 Apr. 62 (4):516-26. [QxMD MEDLINE Link].
Hovi P, Andersson S, Järvenpää AL, et al. Decreased bone mineral density in adults born with very low birth weight: a cohort study. PLoS Med. 2009 Aug. 6(8):e1000135. [QxMD MEDLINE Link]. [Full Text].
French AR, Mason T, Nelson AM, et al. Osteopenia in adults with a history of juvenile rheumatoid arthritis. A population based study. J Rheumatol. 2002 May. 29 (5):1065-70. [QxMD MEDLINE Link].
Lucas AR, Melton LJ 3rd, Crowson CS, O'Fallon WM. Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin Proc. 1999 Oct. 74 (10):972-7. [QxMD MEDLINE Link].
Vassilopoulou-Sellin R, Brosnan P, Delpassand A, Zietz H, Klein MJ, Jaffe N. Osteopenia in young adult survivors of childhood cancer. Med Pediatr Oncol. 1999 Apr. 32 (4):272-8. [QxMD MEDLINE Link].
Landin LA. Epidemiology of children's fractures. J Pediatr Orthop B. 1997 Apr. 6 (2):79-83. [QxMD MEDLINE Link].
Klein GL, Herndon DN, Goodman WG, et al. Histomorphometric and biochemical characterization of bone following acute severe burns in children. Bone. 1995 Nov. 17(5):455-60. [QxMD MEDLINE Link].
Klein GL, Herndon DN, Langman CB, et al. Long-term reduction in bone mass after severe burn injury in children. J Pediatr. 1995 Feb. 126(2):252-6. [QxMD MEDLINE Link].
Sadat-Ali M, Al-Elq AH, Sultan O, Al-Turki H, Bukhari R, Al-Mulhim E. Low bone mass due to sickle cell anemia: is it becoming a real issue?. West Afr J Med. 2008 Oct. 27(4):218-23. [QxMD MEDLINE Link].
Bianchi ML, Bardella MT. Bone in celiac disease. Osteoporos Int. 2008 Dec. 19(12):1705-16. [QxMD MEDLINE Link].
Saha MT, Sievänen H, Salo MK, Tulokas S, Saha HH. Bone mass and structure in adolescents with type 1 diabetes compared to healthy peers. Osteoporos Int. 2009 Aug. 20(8):1401-6. [QxMD MEDLINE Link].
Apkon SD, Fenton L, Coll JR. Bone mineral density in children with myelomeningocele. Dev Med Child Neurol. 2009 Jan. 51(1):63-7. [QxMD MEDLINE Link].
Avgeri M, Papadopoulou A, Platokouki H, et al. Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy. J Pediatr Hematol Oncol. 2008 Aug. 30(8):592-7. [QxMD MEDLINE Link].
Coppola G, Fortunato D, Auricchio G, et al. Bone mineral density in children, adolescents, and young adults with epilepsy. Epilepsia. 2009 Sep. 50(9):2140-6. [QxMD MEDLINE Link].
Halton J, Gaboury I, Grant R, et al. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res. 2009 Jul. 24(7):1326-34. [QxMD MEDLINE Link].
Ward LM, Petryk A, Gordon CM. Use of bisphosphonates in the treatment of pediatric osteoporosis. Int J Clin Rheumatol. 2009. 4(6):657-72.
Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2016 Oct 19. 10:CD005088. [QxMD MEDLINE Link].
Brown JJ, Zacharin MR. Safety and efficacy of intravenous zoledronic acid in paediatric osteoporosis. J Pediatr Endocrinol Metab. 2009 Jan. 22(1):55-63. [QxMD MEDLINE Link].
George S, Weber DR, Kaplan P, Hummel K, Monk HM, Levine MA. Short-term safety of zoledronic acid in young patients with bone disorders: an extensive institutional experience. J Clin Endocrinol Metab. 2015 Nov. 100 (11):4163-71. [QxMD MEDLINE Link].
Boyce AM. Denosumab: an emerging therapy in pediatric bone disorders. Curr Osteoporos Rep. 2017 Aug. 15 (4):283-92. [QxMD MEDLINE Link].
Murphy KD, Thomas S, Mlcak RP, Chinkes DL, Klein GL, Herndon DN. Effects of long-term oxandrolone administration in severely burned children. Surgery. 2004 Aug. 136(2):219-24. [QxMD MEDLINE Link].
Hart DW, Herndon DN, Klein G, et al. Attenuation of posttraumatic muscle catabolism and osteopenia by long-term growth hormone therapy. Ann Surg. 2001 Jun. 233(6):827-34. [QxMD MEDLINE Link]. [Full Text].
Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003 Sep 25. 349(13):1216-26. [QxMD MEDLINE Link]. [Full Text].
Winzenberg T, Shaw K, Fryer J, Jones G. Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. BMJ. 2006 Oct 14. 333(7572):775. [QxMD MEDLINE Link]. [Full Text].
Koo W, Walyat N. Vitamin d and skeletal growth and development. Curr Osteoporos Rep. 2013 Sep. 11(3):188-93. [QxMD MEDLINE Link].
Golden NH, Abrams SA, Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics. 2014 Oct. 134 (4):e1229-43. [QxMD MEDLINE Link].
Munns CF, Shaw N, Kiely M, et al. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016 Feb. 101 (2):394-415. [QxMD MEDLINE Link].
MacKelvie KJ, Petit MA, Khan KM, Beck TJ, McKay HA. Bone mass and structure are enhanced following a 2-year randomized controlled trial of exercise in prepubertal boys. Bone. 2004 Apr. 34(4):755-64. [QxMD MEDLINE Link].
Bachrach LK, Sills IN. Clinical report—bone densitometry in children and adolescents. Pediatrics. 2011 Jan. 127(1):189-94. [QxMD MEDLINE Link].

Media Gallery

Prediction of bone loss with biochemical bone markers. Adapted from Ross PD, Knowlton W. Rapid bone loss is associated with increased levels of biochemical markers. (DPD stands for deoxypyridinoline.) J Bone Miner Res 1998 Feb; 13(2): 297-302.

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Table 1. Conditions Associated with Reduced Bone Mass in Children and Adolescents

Genetic conditions

Osteogenesis imperfecta

Idiopathic juvenile osteoporosis

Turner syndrome

Chronic illness

Cystic fibrosis

Connective tissue disorders (lupus, juvenile idiopathic arthritis, juvenile dermatomyositis)

Inflammatory bowel disease, celiac disease

Chronic renal failure

Childhood cancer

Cerebral palsy

Chronic immobilization

Eating disorders, including anorexia nervosa, bulimia nervosa, eating disorders not otherwise specified, and the female athlete triad

Endocrine disorders

Cushing syndrome

Hypogonadism

Hyperthyroidism

Hyperparathyroidism

Growth hormone deficiency

Diabetes mellitus

Medications

Glucocorticoids

Anticonvulsants

Chemotherapy

Leuprolide acetate

Proton pump inhibitors

Selective serotonin reuptake inhibitors

Depot medroxyprogesterone acetate (DMPA)

Table 2. Calcium and Vitamin D Dietary Reference Intakes^[11]

Age	Calcium		Vitamin D
Age	RDA (mg/d) (Intake That Meets Needs of ≥97.5% of Population)	UL (mg/d)^a	RDA (IU/d) (Intake That Meets Needs of ≥97.5% of Population)	UL (IU/d)^a
Infants
0-6 mo	200^b	1000	400^b	1000
6-12 mo	260^b	1500	400^b	1500
1-3 y	700	2500	600	2500
4-8 y	1000	2500	600	3000
9-13 y	1300	3000	600	4000
14-18 y	1300	3000	600	4000

Table 3. Dietary Sources of Calcium

Food	Serving Size	Calories per Portion	Calcium Content (mg)
Dairy foods
Milk
Whole milk	8 oz	149	276
Reduced-fat milk (2%)	8 oz	122	293
Low-fat milk (1%)	8 oz	102	305
Skim milk (nonfat)	8 oz	83	299
Reduced-fat chocolate milk (2%)	8 oz	190	275
Low-fat chocolate milk (1%)	8 oz	158	290
Yogurt
Plain yogurt, low-fat	8 oz	143	415
Fruit yogurt, low-fat	8 oz	232	345
Plain yogurt, nonfat	8 oz	127	452
Cheese
Romano cheese	1.5 oz	165	452
Swiss cheese	1.5 oz	162	336
Pasteurized processed American cheese	2 oz	187	323
Mozzarella cheese, part skim	1.5 oz	128	311
Cheddar cheese	1.5 oz	171	307
Muenster cheese	1.5 oz	156	305
Nondairy foods
Salmon	3 oz	76	32
Sardines, canned	3 oz	177	325
White beans, cooked	1 cup	307	191
Broccoli, cooked	1 cup	44	72
Broccoli, raw	1 cup	25	42
Collards, cooked	1 cup	49	226
Spinach, cooked	1 cup	41	249
Spinach, raw	1 cup	7	30
Baked beans, canned	1 cup	680	120
Tomatoes, canned	1 cup	71	84
Calcium-fortified food
Orange juice	8 oz	117	500
Breakfast cereals	1 cup	100-210	250-1000
Tofu, made with calcium	0.5 cup	94	434
Soy milk, calcium fortified^a	8 oz	104	299

Table 4. Sources of Vitamin D

Food	Serving Size	Vitamin D Content^a (IU)
Natural sources
Salmon
Fresh wild	3.5 oz	600-1000
Fresh farmed	3.5 oz	100-250
Sardines, canned	3.5 oz	300
Mackerel, canned	3.5 oz	250
Tuna, canned	3.5 oz	236
Shiitake mushroom
Fresh	3.5 oz	100
Canned	3.5 oz	1600
Egg, hard-boiled	3.5 oz	20
Vitamin D-fortified foods
Infant formula	1 cup (8 oz)	100
Milk	1 cup (8 oz)	100
Orange juice^b	1 cup (8 oz)	100
Yogurts^b	1 cup (8 oz)	100
Cheeses^b	3 oz	100
Breakfast cereals^b	1 serving	40-100
Pharmaceutical sources in the United States
Vitamin D₂ (ergocalciferol)	1 capsule	50000
Drisdol (vitamin D₂) liquid	1 cc	8000
Supplemental sources
Multivitamin		400, 500, 1000
Vitamin D₃		400, 800, 1000, 2000, 5000, 10,000, 50,000

Table 5. Treatment of Vitamin D Deficiency

Age	Preparation and Dose^a
Infants, 0-12 mo	Vitamin D₂ or D₃ 50,000 IU weekly for 6 wk	or	Vitamin D₂ or D₃ 2000 IU daily for 6 wk
Infants, 0-12 mo	Followed by a maintenance dose of 400-1000 IU daily		Followed by a maintenance dose of 400-1000 IU daily
Children and adolescents, 1-18y	Vitamin D₂ or D₃ 50 000 IU weekly for 6-8 wk	or	Vitamin D₂ or D₃ 2000 IU daily for 6-8 wk
Children and adolescents, 1-18y	Followed by a maintenance dose of 600-1000 IU daily		Followed by a maintenance dose of 600-1000 IU daily

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Author

Manasa Mantravadi, MD, MS Assistant Research Professor in Endocrinology/Diabetology, Department of Pediatrics, Indiana University School of Medicine

Manasa Mantravadi, MD, MS is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Stephanie E Woerner, RN, MSN, FNP-C, CDE Family Nurse Practitioner, Pediatric Endocrinology and Diabetology, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine; Family Nurse Practitioner, MinuteClinic, Inc

Disclosure: Nothing to disclose.

Linda A DiMeglio, MD, MPH Associate Professor of Pediatrics, Section of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine; Director, Type 1 Diabetes Research Team, Riley Hospital for Children at Indiana University Health

Linda A DiMeglio, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Society for Bone and Mineral Research, Endocrine Society, Midwest Pediatric Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Received research grant from: Alexion.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Jatinder Bhatia, MBBS, FAAP Professor of Pediatrics, Medical College of Georgia, Georgia Regents University; Chief, Division of Neonatology, Director, Fellowship Program in Neonatal-Perinatal Medicine, Director, Transport/ECMO/Nutrition, Vice Chair, Clinical Research, Department of Pediatrics, Children's Hospital of Georgia

Jatinder Bhatia, MBBS, FAAP is a member of the following medical societies: Academy of Nutrition and Dietetics, American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Society for Nutrition, American Society for Parenteral and Enteral Nutrition, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Nestle<br/>Serve(d) as a speaker or a member of a speakers bureau for: Nestle<br/>Received income in an amount equal to or greater than $250 from: Nestle.

Additional Contributors

Steven M Schwarz, MD, FAAP, FACN, AGAF Professor of Pediatrics, Children's Hospital at Downstate, State University of New York Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American Association for Physician Leadership, New York Academy of Medicine, Gastroenterology Research Group, American Gastroenterological Association, American Pediatric Society, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Gordon L Klein, MD, MPH Clinical Professor of Orthopedic Surgery and Rehabilitation, University of Texas Medical Branch School of Medicine

Gordon L Klein, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American Gastroenterological Association, American Pediatric Society, American Society for Bone and Mineral Research, American Society for Nutritional Sciences, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Pediatric Osteoporosis Medication

Medication Summary

Bisphosphonate bone-resorption inhibitors