Thacher 1999.

Methods	Study design: parallel randomised controlled trial, randomisation ratio 1:1:1
Participants	Inclusion criteria: children with deformities characteristic of rickets (genu varum, genu valgum and widened wrists) were recruited within and around Jos, Nigeria (population 360,100), through posters, radio announcements and word of mouth. Each child was examined, and a parent or guardian was interviewed. Children aged 1 to 14 years and who had clinical evidence of rickets underwent radiography of the wrists and knees. Rickets was considered active if the epiphyseal plate was wider than normal and there was concave cupping or fraying of the metaphyseal margins on the radiographs. Exclusion criteria: not stated Diagnostic criteria: children were eligible for enrolment if they had a radiographic score of ≥ 2.5 on a validated 10‐point scoring method that assessed the severity of rickets in the growth plates of the distal radius and ulna and around the knee. Setting: hospital Age group: children, adolescents Gender distribution: girls and boys Country where study was performed: Nigeria
Interventions	Interventions: I1: vitamin D 600,000 U intramuscular injection at enrolment and after 12 weeks + calcium carbonate 200 mg tablets – 2 tablets in the morning and 3 in the evening ≥ 30 minutes before eating (total dose, 1000 mg of elemental calcium daily) I2: calcium carbonate 200 mg chewable tablets – 2 tablets in the morning and 3 in the evening at least 30 minutes before eating (total dose, 1000 mg of elemental calcium daily) and an injection of placebo (light mineral oil) at enrolment and after 12 weeks Comparator: vitamin D 600,000 U intramuscular injection at enrolment and after 12 weeks and chewable placebo tablets (candy containing no calcium but similar in appearance to calcium tablets) – 2 in the morning and 3 in the evening ≥ 30 minutes before eating Duration of intervention: 24 weeks Duration of follow‐up: 24 weeks Number of study centres: unclear Run‐in period: none Extension period: none
Outcomes	Outcomes reported Healing of rickets Morbidity Growth pattern
Study details	Study terminated early: no Trial ID: not stated
Publication details	Language of publication: English Funding: non‐commercial funding (supported by a grant from the Thrasher Research Fund, Salt Lake City) Publication status: peer‐reviewed journal
Stated aim for study	Quote: "We report the results of a 24‐week controlled trial to test the hypothesis that calcium supplementation with or without vitamin D is superior to vitamin D alone for the treatment of rickets in Nigerian children."
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Eligible children were randomly assigned in blocks of nine to receive vitamin D, calcium, or both" (p564, 'Study Protocol'). Comment: no details
Allocation concealment (selection bias)	Low risk	Quote: "Medication kits were serially numbered and contained the complete 24‐week treatment for each child. The randomization code was kept at the University of Utah and was not broken until all data had been collected. The medications were dispensed in sealed, opaque packets, and vitamin D or placebo was administered intramuscularly on two occasions by a nurse while the investigators were in a different room" (p564, 'study protocol').
Blinding of participants and personnel (performance bias) – growth pattern	Low risk	Quote: "The medications were dispensed in sealed, opaque packets, and vitamin D or placebo was administered intramuscularly on two occasions by a nurse while the investigators were in a different room". (P564, study protocol). Comment: outcome measure unlikely influenced by potential lack of blinding.
Blinding of participants and personnel (performance bias) – healing of rickets	Low risk	Quote: "The medications were dispensed in sealed, opaque packets, and vitamin D or placebo was administered intramuscularly on two occasions by a nurse while the investigators were in a different room. Children assigned to the vitamin D group received an intramuscular injection of 600,000 U of vitamin D at enrollment and after 12 weeks. They were also provided chewable placebo tablets (candy containing no calcium but similar in appearance to calcium tablets) and instructed to take two in the morning and three in the evening at least 30 minutes before eating. Children assigned to the calcium group were supplied chewable 200‐mg tablets of calcium carbonate and were instructed to take two tablets in the morning and three in the evening at least 30 minutes before eating (total dose, 1000 mg of elemental calcium daily). They were given an injection of placebo (light mineral oil) at enrollment and after 12 weeks. The combination‐therapy group received both vitamin D and calcium in the doses given above." (p564, 'study protocol'). Comment: outcome measure unlikely influenced by potential lack of blinding.
Blinding of participants and personnel (performance bias) – morbidity	Low risk	Quote: "The medications were dispensed in sealed, opaque packets, and vitamin D or placebo was administered intramuscularly on two occasions by a nurse while the investigators were in a different room. Children assigned to the vitamin D group received an intramuscular injection of 600,000 U of vitamin D at enrollment and after 12 weeks. They were also provided chewable placebo tablets (candy containing no calcium but similar in appearance to calcium tablets) and instructed to take two in the morning and three in the evening at least 30 minutes before eating. Children assigned to the calcium group were supplied chewable 200‐mg tablets of calcium carbonate and were instructed to take two tablets in the morning and three in the evening at least 30 minutes before eating (total dose, 1000 mg of elemental calcium daily). They were given an injection of placebo (light mineral oil) at enrollment and after 12 weeks. The combination‐therapy group received both vitamin D and calcium in the doses given above" (p564, 'study protocol'). Comment: outcome measure unlikely influenced by potential lack of blinding.
Blinding of outcome assessment (detection bias) – growth pattern	Low risk	Comment: unclear who assessed growth pattern (height and weight); however, this is an objective measurement and is unlikely to be influenced by absence of blinding.
Blinding of outcome assessment (detection bias) – healing of rickets	Low risk	Quote: radiographs: "Each radiograph was independently scored by three physicians who were unaware of the child's treatment assignment, and the mean value of the three scores was used for the analysis" (p564, 'Data and Sample Collection'). Biochemical: "Biochemical testing was performed by Associated Regional University Pathologists (Salt Lake City)" (p564, 'Biochemical Measurements').
Blinding of outcome assessment (detection bias) – morbidity	Low risk	Comment: unclear who assessed morbidity; however, in the case of this study, the outcome (fractures) was an objective measurement and unlikely to be influenced by absence of blinding.
Incomplete outcome data (attrition bias) – adverse events	Unclear risk	Comment: attrition rates differed between intervention groups (calcium + vitamin D 5%, calcium + placebo 16.7%, vitamin D + placebo 9.8%). Unclear whether the outcome measure was influenced by these attrition rates.
Incomplete outcome data (attrition bias) – growth pattern	Unclear risk	Comment: attrition rates differed between intervention groups (calcium + vitamin D 5%, calcium + placebo 16.7%, vitamin D + placebo 9.8%). Unclear whether the outcome measure was influenced by these attrition rates.
Incomplete outcome data (attrition bias) – healing of rickets	Unclear risk	Comment: attrition rates differed between intervention groups (calcium + vitamin D 5%, calcium + placebo 16.7%, vitamin D + placebo 9.8%). Unclear whether the outcome measure was influenced by these attrition rates.
Incomplete outcome data (attrition bias) – morbidity	Unclear risk	Comment: attrition rates differed between intervention groups. Unclear whether the outcome measure was influenced by these attrition rates.
Selective reporting (reporting bias)	Unclear risk	Comment: protocol for study not available.
Other bias	Low risk	Comment: no other sources of bias were identified.