Severe energy restriction improves weight loss in postmenopausal women; potential risk to hip BMD

In postmenopausal women, severe energy restriction led to greater weight, fat, and whole-body lean mass loss than that achieved with moderate energy restriction, according to results of the TEMPO* Diet trial conducted in Sydney, Australia. However, there was a tendency toward greater loss in total hip bone mineral density (BMD) with severe energy restriction.

“[S]evere energy restriction with a total meal replacement diet in postmenopausal women with obesity induced greater weight loss and approximately 1.5-fold as much loss of whole-body lean mass and thigh muscle area compared with moderate energy restriction over 12 months,” said the authors.

“[However], there was an approximately 2.5-fold greater loss of total hip BMD with severe compared with moderate energy restriction, a difference not accounted for by the greater weight loss.”

Participants in this single-centre study were 101 women aged 45–65 years (mean age 58 years) with a BMI of 30–40 kg/m² (mean 34.4 kg/m²), who were postmenopausal for ≥5 years, and with <3 hours of structured physical activity per week. They were randomized to undergo moderate energy restriction (25–35 percent) with a food-based diet for 12 months or severe energy restriction (65–75 percent) with a total meal replacement diet for 4 months followed by moderate energy restriction for 8 months. Participants in both groups were prescribed a protein intake of 1 g/kg of actual body weight per day, and physical activity was encouraged.

At 12 months after intervention initiation, participants on severe energy restriction experienced greater weight loss compared with those on moderate energy restriction (estimated marginal mean [EMM], -15.3 vs -8.4 kg; p<0.001; effect size**, -6.6 kg), with a 2.5- to threefold greater likelihood of clinically significant weight loss (≥10 percent) with the severe vs moderate intervention (82.0 vs 27.5 percent; p<0.001). [JAMA Netw Open 2019;2:e1913733]

Compared with the moderate intervention, the severe intervention also had a greater impact on whole-body lean mass loss (EMM, -3.2 vs -2.1 kg; p=0.005; effect size, -1.2 kg), and thigh muscle area loss (EMM, -8.2 vs -3.9 cm²; p<0.001; effect size, -4.2 cm²) at 12 months (both proportional to total weight loss), as well as BMI (-5.81 vs -3.17 kg/m²; p<0.001).

Individuals on the severe intervention also had significantly lower whole-body fat mass, abdominal subcutaneous and visceral adipose tissue volume, and waist-hip ratio at 12 months than those on the moderate intervention.

However, a greater loss of total hip BMD was noted with the severe vs moderate intervention at 12 months (EMM, -0.032 vs -0.015 g/cm²; p=0.002; effect size, -0.017 g/cm²).

Lumbar spine and whole-body BMD loss did not significantly differ between groups, nor did muscle strength, as determined by handgrip.

Eight adverse events (AEs) – six and two in the severe and moderate intervention groups, respectively, none serious – were reported. The AEs in the severe intervention group were related or possibly related to the intervention; neither in the moderate group was intervention-related.

The impact on hip BMD

“The consequences of accelerated BMD loss with a severely energy-restricted dietary obesity treatment are clinically concerning, especially if BMD loss continues beyond the 12-month intervention,” said the authors.

In this study, the total hip BMD loss in the moderate intervention group (1.3 percent decrease over 12 months) was similar to the annual hip BMD loss in the early postmenopausal period. Conversely, the 3.3 percent reduction with the severe intervention was more than twice that of the estimated annual loss and persisted despite weight loss plateau, they said.

“[T]his bone loss must be considered in light of the beneficial effects of substantial weight loss on other health outcomes and health care costs … the current trial should not discourage the use of total meal replacement diets as a treatment for obesity in postmenopausal women,” they said.

Instead, they recommended caution when implementing severe energy-restriction diets in postmenopausal women, particularly those with osteopenia or osteoporosis, and called for research to establish methods of preventing BMD loss.

They also noted that the use of DXA to assess BMD loss may have affected the findings. “DXA assesses bone quantity and not bone quality … or osteoporotic fracture incidence, and it is possible that, despite BMD loss, bone quality and strength may have been preserved in our participants,” they said.