Table 2

Semiquantitative synthesis with modified GRADE rating

OutcomeStudies (n)Participants (n)Follow-up (years)Study designStudy limitationsInconsistencyIndirectnessImprecisionModified GRADE ratingDirection and magnitude
(without stratifying for age)
Lumbar BMD35 39 40 42 46–50 52 58 62–66 71 73–75 77–79 2344841–20+++XXXX+CHC use may not be associated with lumbar BMD
Femoral Neck BMD35 40 42 48 50 52 58 62–64 66 71 75 78 1433141–20++++XXXX+CHC use may not be associated with femoral neck BMD
Whole Body BMD39 42 45 58 64 73 77 82 819140.8–20+++XXXXX+Association between CHC use and whole body BMD is unclear
D-PYD40 46 47 49 65 67 66681–2+++XXXX+Association between CHC use and DPD is unclear
CTX41 45 51 61 82 51800.08–1+++XXXX+Association between CHC use and CTX is unclear
LBM43 70 73 76 82 57130.18–2.2++++XXXXX+Association between CHC use and LBM is unclear
Lumbar BMC35 58 62 64 77 512301–20+++XXXXX+Association between CHC use and lumbar BMC is unclear
Whole body BMC35 58 64 74 77 513211–20++++XXXX+Association between CHC use and whole body BMC is unclear
Any fracture34 37 72 81 41 663 0622.5–26+++X++CHC use may ↑ fracture risk by 1.20 times (RR 95% CI 1.08 to 1.34)
P1NP45 51 61 83 41190.08–0.8+++XXXX+Association between CHC use and P1NP is unclear
PYD46 47 49 65 42331++XXX+Association between CHC use and PYD is unclear
BAP40 41 45 51 43970.08–1+++XXXXX+Association between CHC use and BAP is unclear
BGP46 47 49 65 42331++XXXX+Association between CHC use and BPG is unclear
Radius BMD35 48 62 80 46551–5++++XXX+Association between CHC use and radius BMD is unclear
Total Hip BMD39 73–75 49332–7++++XXXX+CHC use may not be associated with Total Hip BMD
TKA53 55 60 31 345 0786–15+++X++CHC use may ↑ TKR risk by 1.36 times (RR 95% CI 1.00 to 1.86)
  • ✓, no limitation; +++, moderate-quality evidence; +, very low quality evidence; ++, low-quality evidence; ++++, high-quality evidence; BAP, bone alkaline phosphatase; BGP, Osteocalcin; BMC, bone mineral content; BMD, bone mineral density; CHC, combined hormonal contraceptive; CTX, C-terminal peptide; D-PYD, deoxypyridinoline; GRADE, Grading of Recommendations Assessment, Development and Evaluation; LBM, lean body mass; P1NP, procollagen type 1 terminal peptide; RR, risk ratio; TKA, total knee arthroplasty; X, serious limitation; XX, very serious limitation.