Table 1.
Studies included in the systematic review.
| First Author | Year | Study Design | Sample | Age | Baseline BMI | Duration of Illness | Follow-Up | Site | Intervention Outcome | Change in BMD | Quality Score |
|---|---|---|---|---|---|---|---|---|---|---|---|
| A. Studies in adolescent females with anorexia nervosa | |||||||||||
| 1. No significant change in BMD after weight gain/restoration | |||||||||||
| Kooh et al. [33] | 1996 | Prospective controlled | N = 12 completers from an original sample of n = 22 | 14–21 years | 15.9 ± 2.2 kg/m2 | Not available | Non-standardized, between 7 and 26 months; Mean follow-up 14.1 ± 5.4 months | Lumbar spine; Femoral neck | Weight gain, mean 4.9 kg | No change in BMD | 5 ** |
| Muňoz et al. [19] | 2002 | Prospective non-controlled | N = 38; N = 12 completers | 17.4 ± 1.5 years | −1.4 ± 0.5 SD | Not available | 12 months | Lumbar spine (L2–L4) | Weight gain, expressed as SD BMI | No change in BMD from baseline to follow-up | 5 * |
| Golden et al. [34] | 2002 | Prospective non-controlled | N = 28; N = 25 completers | 13–21 years | 16.9 ± 1.5 kg/m2 | 21.9 ± 20.6 months | 12 months | Lumbar spine (L2–L4) and femoral neck | Weight gain, mean 7.1 ± 9.0 kg | No significant improvement in lumbar spine or femoral neck BMD from baseline to follow-up | 6 * |
| Soyka et al. [35] | 2002 | Prospective controlled study | N = 19 | 12.9–17.8 years | 16.4 ± 0.5 kg/m2 | 14.0 ± 3.0 months | 12 months | Total body and lumbar BMD | Weight restoration, BMI = 18.9 ± 0.6 kg/m2 in 11 participants | Lumbar BMD remained lower than that in controls | 6 ** |
| Compston et al. [36] | 2006 | Prospective non-controlled | N = 26; N = 21 completers | 13–20 years | 14.2 ± 1.7 kg/m2 | Not available | 12 months | Lumbar spine and proximal femur BMD | Weight gain during treatment ~10 kg | No significant changes in BMD of lumbar spine, femoral neck, total hip or total body | 7 * |
| Oświęcimska et al. [37] | 2007 | Prospective non-controlled | N = 18 | 11.5–18.1 years | 15.8 ± 2.1 kg/m2 | 14.9 ± 13.6 months | Non-standardized, mean 19.4 ± 5.6 months | Total body and lumbar spine BMD | Weight restoration (BMI ≥ 18.5 kg/m2) and resumption of menstrual cycle in 9/18 patients | No significant changes in mean BMD of total body or lumbar spine; Significant reduction in total body BMD z-score at follow-up | 6 * |
| Misra et al. [38] | 2008 | Prospective controlled | N = 34; N = 14 | 12–18 years | 16.6 ± 1.2 kg/m2 | 11.2 ± 12.4 months | 12 months | Lumbar and total BMD | Weight restoration | Stabilization of BMD but no improvement | 7 ** |
| Franzoni et al. [39] | 2014 | Prospective non-controlled | N = 79; N = 46 completers | 11–22 years | 16.3 ± 1.3 kg/m2 | 27.8 ± 23.9 months | 12 months | Lumbar BMD | Weight gain (ΔBMI = +1.29 ± 1.85 kg/m2) | No significant changes in lumbar BMD z-score from baseline to one-year follow-up | 5 * |
| 2. Improvement/normalisation in BMD after weight gain/restoration | |||||||||||
| Bachrach et al. [40] | 1991 | Prospective non-controlled | N = 15 | 16.7 ± 2.4 years | 15.8 ± 1.7 kg/m2 | Not available | 12–16 months | Spine (L2–L4) and whole BMD | Weight gain of 4.7–17.4 kg in 9 patients | Increase in whole body BMD No changes in the spine Persistent osteopenia | 4 * |
| Jagielska et al. [41] | 2001 | Prospective non-controlled | N = 42; N = 11 completers | 10.8–22.2 years | 14.7 ± 2.4 kg/m2 | 14.1 ± 17.4 months | 28 months | Total and lumbar spine BMD as absolute value and z-score | Weight gain, from BMI 14.7 ± 5.4 kg/m2 at baseline to 19.8 ± 3.0 kg/m2 | Increase in lumbar and total BMD after only 21 months of follow-up | 5 * |
| Castro et al. [42] | 2001 | Prospective non-controlled | N = 108; N = 23 | 12–17 years | 16.0 ± 1.1 kg/m2 | 10.0 ± 5.4 months | Non-standardized, between 6 and 30 months. Mean follow-up 15.4 ± 6.1 months | Lumbar spine (L2–L4) and femoral neck | Weight restoration, BMI > 19 kg/m2 | Increase in both lumbar spine and femoral neck BMD. Normalization of BMD in 4 patients | 5 * |
| Bass et al. [43] | 2005 | Retrospective non-controlled | N = 13 | 13.4–18 years | 15.3 ± 0.8 kg/m2 | 19.0 months | 40 months | Total and lumbar spine BMD | Weight restoration | Normalization of total body BMD. ~80% improvement in lumbar spine BMD | 5 * |
| Golden et al. [22] | 2005 | Prospective non-controlled | N = 17; N = 15 completers | 13–21 years | 16.4 ± 1.3 kg/m2 | 34.7 ± 28.0 months | 12 months | Lumbar (L1–L4) and femoral neck BMD | Weight gain during treatment, ~16.2% | Increase in lumbar and femoral neck BMD; Normalization in less than one-third of patients | 5 * |
| Mika et al. [44] | 2007 | Prospective non-controlled | N = 19 | Mean 14.4 ± 1.6 years | 14.2 ± 1.4 kg/m2 | 10.6 ± 6.7 months | 24 months | Lumbar and femoral neck BMD | Weight gain, and 10/19 patients maintained restored weight (BMI ≥ 10th percentile) | Small improvements in BMD of lumbar and femoral neck from baseline to follow-up | 6 * |
| do Carmo et al. [45] | 2007 | Retrospective non-controlled | N = 68; N = 15 completers | 13–19 years | 15.1 ± 1.3 kg/m2 | Not available | 90 months | Total body, femoral neck and lumbar (L1–L4) BMD | Weight restoration and maintenance in 11/15 patients (BMI ≥ 18.5 kg/m2) | Increase in mean t- and z- BMD scores of the lumbar (L2–L4) and femoral neck. | 4 * |
| Schulze et al. [46] | 2010 | Retrospective non-controlled | N = 52 | 10–19 years | 14.7 ± 1.9 kg/m2 | Not available | >36 months | Total body BMD | Weight restoration, BMI ≥ 17.5 kg/m2 in 26/52 participants | Significant increase in total body BMD (ΔBMD = +0.08 ± 0.07) | 5 * |
| Misra et al. [47] | 2011 | Prospective controlled | N = 110; N = 30 | Mean 16.5 ± 0.2 years | 17.4 ± 0.9 kg/m2 | Not available | 18 months | Spine (L1–L4) and hip BMD | Weight gain | Increase in lumbar BMD, which remained lower than that in normal-weight control girls. | 7 ** |
| 3. Reduction in BMD after weight gain | |||||||||||
| Stone et al. [48] | 2006 | Retrospective non-controlled | N = 30 | Mean 14.6 years | 14.9 kg/m2 | Not available | 12 months | Total body, femoral neck and lumbar (L1–L4) BMD | Weight gain during treatment, ~19% in premenarchal subjects and ~5.6% in postmenarchal subjects | Further reduction in all BMD measures | 3 * |
| B. Studies in adolescent males with anorexia nervosa | |||||||||||
| Castro et al. [10] | 2002 | Prospective non-controlled | N = 20; N = 15 completers | 12–17 years | 16.2 ± 1.2 kg/m2 | 12.5 ± 6.4 months | Non-standardized, between 6 and 24 months | Lumbar spine (L2–L4) and femoral neck | Weight gain group, BMI < 19 kg/m2 (N = 6); Weight restoration group, BMI ≥ 19 kg/m2 (N = 9) | Further BMD loss of −3.2%/year at lumbar spine and −6.4%/year at femoral neck in weight gain group. BMD gain of +7.8%/year at lumbar spine and +6.7%/year at femoral neck in weight restoration group | 5 * |
BMD: bone mineral density. * NICE guidelines checklist: Yes = 1, No (not reported, not available) = 0; Total score, 8; ≤3, poor quality; 4–6, fair quality; ≥7, good quality. ** Newcastle–Ottawa Scale (NOS) for longitudinal case control studies. Yes = 1, No (not reported, not available) = 0; Studies with scores of 0–3, 4–6, 7–9 were considered as low, moderate and high quality, respectively.