Table 1.

Characteristics of Included Studies

			Glucocorticoid exposure			Bisphosphonate exposure
Author [country]	Study design	Sample, n (age)a	Pharmacologic agent(s)	Dose, mean	Duration, mean	n (%) exposed	Pharmacologic agent(s)	Administration route	Dose, mean	Duration, mean
Case et al. [UK]10	Case study	Case: 11 y	DFZ and PRED	• DFZ: 0.7 mg/kg/d • PRED: 0.8 mg/kg/d	6.3 y	1 (100)	ZLN	IV	0.05 mg/kg	<6 mo (1 IV infusion)
Gordon et al. [CAN]11	Retrospective cohort study	44 (median age: 13 y, range: 7–23 y)	DFZ and/or PDN	NR	>1 y	16 (36)	ALN, CLO, and/or PAM	NR	NR	6 yc
Hawker et al. [CAN]12	Nonrandomized, uncontrolled before-and-after trial	16 (mean age: 11 y, range: 7–16 y)	DFZ	0.69 mg/kg/d	2.6 y	16 (100)	ALN	Oral	0.08 mg/kg/d	2 y
Houston et al. [USA]13	Retrospective cohort study	19 (age NR)d	DFZ and/or PDN	NR	NR	19 (100)e	ALN	Oral	35 mg and/or 70 mg weekly	3.4 y
Ivanyuk et al. [CH]14	Case series	• Case 1: 14 y • Case 2: 13 y	NR	NR	Case 1: 5 y Case 2: 9 y	2 (100)	ZLN	IV	• Case 1: 0.04 mg/kg • Case 2: 0.02 mg/kg	• Case 1: <12 mo (2 IV infusions) • Case 2: <6 mo (1 IV infusion)
Joseph et al. [UK]4	Retrospective cohort study	520 (age NR)f	DFZ and/or PRED	NR	4.0 y	NRf	NR	Oral and IV	NR	NR
Lemon et al. [UK]15	Case series	• Case 1: 11 y • Case 2: 15 y	DFZ	18 mg/d	NR	2 (100)	ZLN	IV	• Case 1: 0.025 mg/kg • Case 2: 0.05 mg/kg	<6 mo (1 IV infusion)
Lim et al. [AUS]27	Case series	9 (mean age: 13 y, range: 9–15 y) (see article for case-specific details)	DFZ or PRED	• DFZ: 0.9 mg/kg/dg • PRED: 0.75 mg/kg/dg	6.8 y (see article for case-specific details)	9 (100)	ZLN	IV	0.12 mg/kg/y (see article for case-specific details)	2.3 y (see article for case-specific details)
Misof et al. [CAN]16	Prospective cohort study	9 (mean age: 11 y, range: 8–14 y)h	DFZ or PDN	• DFZ: 0.6 mg/kg/d • PDN: 0.3 mg/kg/d	3.4 y	9 (100)	PAM or ZLN	IV	• PAM: 9 mg/kg/y • ZLN: 0.05–0.10 mg/kg/y	2.4 y
Moretti et al. [IT]17	Retrospective cohort study	8 (mean age: 19 y, range NR)	DFZ	15 mg/d	11.5 yc	8 (100)	NER	IM injection	25 mg/mo	12 mo
Nasomyont et al. [USA]18	Retrospective cohort study	52 (median age: 12 y, range: 8–20 y)	DFZ or PDN	• DFZ: 0.9 mg/kg/dg • PRED: 0.75 mg/kg/dg	4.7 y	52 (100)	ALN	Oral	17.5 mg/wk (age <7 y) and 35 mg/wk (age ≥8 y)g	≤5 y
Palomo Atance et al. [ES]19	Case series	• Case 1: 8 y • Case 2: 16 y	DFZ	• Case 1: 0.7 mg/kg/d • Case 2: 1.0 mg/kg/d	NR	2 (100)	ALN	Oral	10 mg/d	• Case 1: 2.1 y • Case 2: 1.2 y
Ronsley et al. [CAN]20	Retrospective cohort study	68 (mean age: 13 y, range: NR)	DFZ or PDN	• DFZ: 0.9 mg/kg/d (maximum 36 mg) • PDN: 0.7 mg/kg/d	8.5 y	32 (47)	PAM and/or ZLN	IV	• PAM: 9 mg/kg/y • ZLN: 0.10 mg/kg/y	4.2 y
Sbrocchi et al. [CAN]21	Retrospective cohort study	5 (mean age: 10 y, range: 9–12 y)	DFZ	0.9 mg/kg/d	2.8 y	5 (100)	PAM or ZLN	IV	• PAM: 9 mg/kg/y • ZLN: 0.10 mg/kg/y	2 y
Srinivasan et al. [UK]22	Nonrandomized case-control trial	51 (mean age: 9 y, range: NR)	DFZ or PRED	NR	3.3 yc	36 (71)i	RIS	Oral	35 mg/wkj	3.6 y
Tian et al. [USA]23	Retrospective cohort study	54 (median age: 11 y, range: 6–17 y)	NR	NR	4.0 yc	54 (100)k	ALN	Oral	17.5 mg/wk (age <7 y) and 35 mg/wk (age ≥8 y)g	6.0 yc
Ward et al. [multinationalb]24	Randomized controlled trial	34 (mean age: 13 y, range: 9–17 y)l	NR	NR	≥1 dose within 1 y of trial	18 (53)m	ZLN	IV	0.05 mg/kg (maximum 5 mg) once every 6 mo	1 y
Zacharin et al. [AUS/NZ]25	Randomized controlled trial	62 (mean age: 10 y, range: 6–16 y)n	DFZ or PRED	NR	≥3 mo	31 (50)n	ZLN	IV	• Dose 1 and 2 at 0.025 mg/kg (at 0 and 3 mo) • Dose 3, 4, and 5 at 0.05 mg/kg (at 6, 12, and 18 mo)	2 y
Zheng et al. [CN]26	Prospective cohort study	52 (mean age: 10 y, range: 5–16 y)	PRED	0.66 mg/kg/d	21 mo	17 (33)	ALN	Oral	70 mg/wk	24 mo
						18 (35)	ZLN	IV	5 mg/y	24 mo

Abbreviations: ALN = Alendronate; AUS = Australia; CAN = Canada; CH = Switzerland; CLO = Clodronate; CN = China; DFZ = Deflazacort; DMD = Duchenne muscular dystrophy; ES = Spain; IM = Intramuscular; IT = Italy; IV = Intravenous; NER = Neridronate; NR = Not reported; NZ = New Zealand; PAM = Pamidronate; PDN = Prednisone; PRED = Prednisolone; RIS = Risedronate; SQ = Subcutaneous; UK = United Kingdom; USA = United States of America; ZLN = Zoledronate.

^aNumber of patients treated with glucocorticoids (age at study baseline or bisphosphonate initiation).

^bCanada, Australia, the United Kingdom, South Africa, Russia, and Hungary.

^cMedian.

^dA proportion of patients receiving bisphosphonates were not treated with glucocorticoids.

^eNineteen of 29 and 13 of 29 patients treated with bisphosphonates had areal bone mineral density measurements at the total hip and lumbar spine, respectively, at both baseline and the follow-up visit.

^fThe proportion of patients treated with bisphosphonates (n = 47) also treated with glucocorticoids is not reported.

^gStarting dose.

^hOne patient was not treated with glucocorticoids.

ⁱBone mineral density measurements were only available for a subset of the total sample (see article for details).

^jOne mg/kg/wk for patients weighting <20 kg.

^kMeasures of areal bone mineral density at the lumbar spine and whole body were only available for 51 and 49 patients, respectively.

^lThirteen patients diagnosed with DMD (38% of the total cohort).

^mSix patients diagnosed with DMD (33% of all exposed to bisphosphonates).

ⁿFourteen patients withdrew before study completion (5 treated with bisphosphonates and 9 controls). In total, 56 patients completed the 24-mo follow-up (27 treated with zoledronate).