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Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The physiological mechanism for the development of NF1-related bone abnormal turnover is still unclear. A meta-analysis was performed to investigate the effects of NF1 on bone mineral density (BMD) and osseous metabolic indices in order to provide clinical evidence for the pathogenesis of the associated skeletal deformities. A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed/Medline and Web of Science databases from the date of inception of each database through to 10 September 2023. Specific inclusion and exclusion criteria were applied for the identification of studies examining the effects of NF1 on bone strength and metabolism. The Newcastle-Ottawa and Jadad scales were applied to assess the quality of the included studies. RevMan 5.3 software was used for the analysis of the data, and MedCalc was applied to examine publication bias. Overall, 13 studies met the inclusion criteria comprised of 5 cross-sectional, 6 case-control and 2 retrospective studies. 703 patients and 973 healthy subjects formed the NF1 and control group, respectively. The results of the meta-analysis displayed that lumbar (SMD = −3.85, 95%CI = −7.53 to −0.18, Z = 2.05, p = 0.04) and femoral (SMD = −4.78, 95%CI = −8.86 to −0.69, Z = 2.29, p = 0.02) BMD was reduced in the NF1 group. Both in children and adults the serum levels of 25 hydroxyvitamin D3 were also decreased in NF1 group, but without any statistical significance (SMD = −0.62, 95%CI = −1.34 to −0.11, Z = 1.66, p = 0.10). Serum Parathyroid hormone (PTH) (SMD = 0.73, 95%CI = 0.31 to 1.15, Z = 3.43, p = 0.0006) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.82, 95%CI = 0.33 to 1.30, Z = 3.29, p = 0.001) were elevated in NF1 patients, while serum calcium (SMD = −0.10, 95%CI = −0.74 to 0.53, Z = 0.32, p = 0.75) phosphorous (SMD = 0.33, 95%CI = −0.38 to 1.05, Z = 0.92, p = 0.36), alkaline phosphatase (ALP) (SMD = −0.36, 95%CI = −0.77 to 0.05, Z = 1.71, p = 0.09), osteocalcin (SMD = 1.81, 95%CI = −0.37 to −3.98, Z = 1.63, p = 0.10) and bone formation markers (SMD = 0.28, 95%CI = −0.37 to −0.94, Z = 0.85, p = 0.39) were not. NF1 is associated with decreased BMD at the lumbar spine and femur. Taking into account that the serum levels of PTH, CTX were increased whereas the concentrations of vitamin D, calcium, phosphorous, ALP, osteocalcin and bone formation markers were not altered significantly in the NF1 patients compared with the healthy subjects, a vitamin D independent dysregulated bone cellular activity could be considered. Registered on PROSPERO (CRD42023424751). • The meta-analysis provided consistent evidence for the correlation between Neurofibromatosis-1 and low Bone Mineral Density • The comparison of vitamin D, calcium, phosphorous between Neurofibromatosis-1 and healthy individuals didn't reveal statistical difference • Alkaline phosphatase, osteocalcin and bone formation markers were not altered in Neurofibromatosis-1 • Osteoclastic markers were increased in the subjects of Neurofibromatosis-1 group • Our results indicated a vitamin D independent dysregulated bone cellular activity [ABSTRACT FROM AUTHOR]