Table 1 Effect on vertebral fracture rates (from randomized controlled trials)   Osteopenia Osteoporosis (without prevalent vertebral fractures) Established osteoporosis (with prevalent vertebral fractures) Raloxifene ● ■ ■ Alendronate NA ■ ■ Risedronate NA ● ■ Ibandronate NA ■ ■ Zoledronate NA ■ ■ SB202190 Teriparatide NA NA ■ Strontium ranelate ● ■ ■ Denosumab NA ■ ■ NA No evidence available ■ Denotes a preplanned analysis in the entire study population ● Denotes

a post hoc analysis Table 2 Effect on nonvertebral/hip fracture rates (from randomized controlled trials) MEK inhibitor side effects   Nonvertebral Hip Osteoporosis (without prevalent vertebral fractures) Established osteoporosis (with prevalent vertebral fractures) Osteoporosis (without prevalent vertebral fractures) Established osteoporosis (with prevalent vertebral fractures) Raloxifene NA ● NA NA Alendronate ■ ■ NA ■ Risedronate NA ■ NA ■ Ibandronate NA ● NA NA Zoledronate ■ NA ■ NA Teriparatide NA ■ NA NA Strontium Ranelate ● ■ ● ▲ Denosumab ■ NA ■ ICG-001 NA NA no evidence available ■ Denotes a preplanned analysis in the entire study population ▲ Denotes a preplanned analysis on a subset

of the study population ● Denotes a post hoc analysis Calcium and vitamin D supplementation should be a first-line strategy for the management of osteoporosis. Based on the very low mean dietary intake of calcium in the Belgian population, a systematic pharmacological supplementation (1,000–1,200 mg of calcium ion daily) in postmenopausal women appears to be an appropriate strategy (unless an individual dietary assessment reveals a satisfactory intake). The high prevalence of vitamin D deficiency in elderly Belgian subjects, combined

with the low marginal cost of a calcium–vitamin D supplementation compared with calcium alone, suggest that, after the age of 65, calcium and (800–1,000 IU) vitamin D should be systematically offered to all postmenopausal women, either alone or, if needed, in combination with another therapeutic regimen. HRT can no longer be considered as a first-line treatment for osteoporosis. It should only be considered in women experiencing Non-specific serine/threonine protein kinase climacteric symptoms, for the shortest possible duration and with the lowest effective doses. Selective-estrogen receptor modulators are a first-line option for women with low BMD, with or without fractures. Their effect on vertebral fracture is unequivocal, across different degrees of skeletal fragility, ranging from osteopenia to severe osteoporosis. Evidence of antifracture efficacy against nonvertebral fractures is limited to a post hoc analysis performed in a high-risk subset of the population. Breast benefits have been documented and should be taken into account when assessing the overall risk/benefit ratio of SERMs. Bisphosphonates reduce vertebral, nonvertebral, and hip fractures in women with established osteoporosis (low BMD and prevalent fractures).