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Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF

Jessica Pepe 1Jean-Jacques Body 2Peyman Hadji 3Eugene McCloskey 4Christian Meier 5Barbara Obermayer-Pietsch 6Andrea Palermo 7Elena Tsourdi 8M Carola Zillikens 9Bente Langdahl 10Serge Ferrari 11

Affiliations expand

J Clin Endocrinol Metab doi: 10.1210/clinem/dgaa306. 

Abstract

Context: Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking, due to few studies carried out in this population.

Design: ECTS and IOF convened a working group to produce an updated review of literature published after 2017 on this topic.

Results: Fragility fractures in PW are rare and mostly due to secondary osteoporosis, i.e. in presence of an underlying disease such as hormonal, inflammatory or digestive disorders. In absence of another disorder, low bone density (BMD) together with fragility fractures qualifies as «idiopathic osteoporosis». In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities.BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-TNF alfa improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed.

Conclusions

Underlying diseases are common among premenopausal women with osteoporosis. The diagnosis of osteoporosis in premenopausal women requires not only the presence of low BMD but also evidence of bone fragility, which reflects an abnormal bone microarchitecture . In contrast to post-menopausal women, however, bone turnover is not necessarily elevated in premenopausal osteoporosis, at least not when estrogen deficiency is absent. In the rare cases of idiopathic osteoporosis, new evidence from HR-pQCT and genetic evaluations suggest that the primary deficit is in the osteoblast function, but the exact mechanisms remains unknown. Identifying premenopausal women at risk of fracture remains challenging and further HR-pQCT studies may contribute to understand the importance of bone microstructural alterations in this population, although the clinical use of this technology remains uncertain. Morover, we need additional research to establish normative databases for premenopausal women, so that in the future, HR-pQCT will be more useful clinically. Meanwhile, DXA with VFA, common clinical risk factors as well disease- and drug-related risk factors (in case of secondary osteoporosis) must all be taken into account to properly assess fracture risk in these women, as recently illustrated in diabetes (47).

The treatment of underlying causes of secondary osteoporosis is beneficial not only with regards to BMD but also to bone microstructure. In case treatment of the underlying cause is not successful and/or in presence of severe osteoporosis, antiresorptive and bone forming drugs can be used as in postmenopausal osteoporosis. Further RCTs with fracture reduction as a primary outcome are needed to better tailor treatment to patients at high risk of fracture. Although some new data on bisphosphonate safety in women at childbearing potential are now available, more robust evidence is needed as well as data on denosumab and bone forming drugs like teriparatide, abaloparatide and romosozumab in humans.