Abnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement

Abstract

Background: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking.

Objective: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI.

Method: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years.

Results: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm² and 0.0070 (p<0.05), respectively.

Conclusion: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes.

Keywords: appendicular lean mass; body composition; bone mineral density; osteoporosis; premature ovarian insufficiency; trabecular bone score.

Figure 1

Study scheme. The bone & body composition parameters were compared between 25 s-POI and 35 i-POI patients from the Monash Health POI cohort and 60 age & BMI matched controls from the GOS. *27 patients had non-breast cancer malignancy, 27 patients had oophorectomies and 17 had chemo ± radiotherapy. DXA, Dual energy Xray Absorptiometry; POI, Premature ovarian insufficiency; ERT, Estrogen replacement therapy; a-BMD, aerial bone mineral density; LS, Lumbar spine; FN, Femoral neck; TBS, Trabecular bone score; TFM, Total fat mass; ALM, Appendicular lean mass; GOS, Geelong Osteoporosis Study.

Figure 2

Prevalence of low TBS. Low TBS was defined as TBS <1.302 [including both partially degraded & degraded TBS (18)].

Figure 3

Longitudinal changes in bone and body composition parameters in women (including participant with L1 fracture receiving antiresorptive therapy; n=24) with premature ovarian insufficiency stratified by estrogen replacement therapy (ERT) use. Scatterplots (A–E) shows Δ/Year (95%CI) with p values for skeletal and body composition changes for women who had continuous ERT (solid circles) and interrupted ERT (hollow circles) with solid and dashed regression lines indicate the mean annual change in parameter for continued ERT and interrupted ERT, respectively. The respective changes were (A) LS BMD Δ/Year (95%CI) 0.0019 (-0.0019, 0.0058) p = 0.32, and -0.0035 (-.0014, 0.0067), p = 0.50 (B) FN BMD Δ/Year (95%CI) 0.0016 (-0.0038,0.00059), p = 0.15 and -0.020 (-0.037, -0.0024), p = 0.025 (C) TBS Δ/Year (95%CI) 0.0032 (-0.0019, 0.0083), p = 0.23, and -0.0070 (-0.011, -0.0020), p=0.007 (D) ALMI Δ/Year (95%CI) 47.29 (25.35, 69.23) p=<0.001 and -590.48 (-1754.61, 573.64), p=0.32 (E) TFMI Δ/Year (95%CI) 37.05 (-96.59, 170.69) p=0.59 and -154.22 (-537.42, 228.99) p=0.43 ERT, estrogen replacement therapy; LS, lumbar spine; BMD, bone mineral density; FN, femoral neck; TBS, trabecular bone score; ALMI, appendicular lean mass index; TFMI, total fat mass index.