PMID- 32710428
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20211025
IS  - 1544-2241 (Electronic)
IS  - 1544-1873 (Linking)
VI  - 18
IP  - 5
DP  - 2020 Oct
TI  - Diabetes and Bone Fragility: SGLT2 Inhibitor Use in the Context of Renal and 
      Cardiovascular Benefits.
PG  - 439-448
LID - 10.1007/s11914-020-00609-z [doi]
AB  - PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) has been shown to negatively 
      impact bone quality and increase fracture risk. While the pathophysiology of bone 
      fragility in T2DM is not clear and likely multifactorial, medications used to 
      treat T2DM are increasingly scrutinized for their potential role in aberrant bone 
      metabolism. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are gaining 
      popularity in patients with T2DM. In addition to lowering blood glucose, there is 
      evidence that these drugs offer cardiac and renal benefit to individuals with 
      T2DM, leading to FDA-approved indications for use in at-risk individuals. At the 
      same time, there remain concerns that SGLT2 inhibitors, specifically 
      canagliflozin, have adverse effects on bone metabolism and increase fracture risk 
      in T2DM. This review seeks to further clarify the impact of these agents on the 
      skeleton. RECENT FINDINGS: SGLT2 inhibitors may indirectly disrupt calcium and 
      phosphate homeostasis, contribute to weight loss, and cause hypotension, 
      resulting in bone mineral density (BMD) losses and increased falls. The true 
      long-term impact of SGLT2 inhibitors on the diabetic skeleton is still unclear; 
      this review summarizes the results in studies investigating the impact of SGLT2 
      inhibitors on fracture risk in T2DM. Whereas studies performed with dapagliflozin 
      and empagliflozin have not shown an increased risk of bone fractures compared 
      with placebo, some studies have shown increased markers of bone turnover and 
      reduced bone mineral density with canagliflozin treatment. While an increased 
      fracture risk was observed with canagliflozin in the CANVAS trial (HR 1.26; 95% 
      CI 1.04, 1.52), an increased risk was not seen in the CANVAS-R (HR 0.86) or 
      CREDENCE (HR 0.98) trials. There is substantial evidence of the cardiac and renal 
      protective benefits of SGLT2 inhibitors. There does not appear to be an increased 
      fracture risk with the use of dapagliflozin or empagliflozin. Given the possible 
      association between canagliflozin and adverse bone outcomes described in CANVAS, 
      canagliflozin use should be pursued in individuals with T2DM only after careful 
      consideration of the individual's skeletal risk.
FAU - Jackson, Kristen
AU  - Jackson K
AD  - School of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns 
      Hopkins University, 5501 Hopkins Bayview Circle, 2A62, Baltimore, MD, 21224, USA.
FAU - Moseley, Kendall F
AU  - Moseley KF
AUID- ORCID: 0000-0003-2500-2312
AD  - School of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns 
      Hopkins University, 5501 Hopkins Bayview Circle, 2A62, Baltimore, MD, 21224, USA. 
      kmosele4@jhmi.edu.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Osteoporos Rep
JT  - Current osteoporosis reports
JID - 101176492
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Phosphates)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - HDC1R2M35U (empagliflozin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Accidental Falls
MH  - Benzhydryl Compounds/therapeutic use
MH  - *Bone Density
MH  - *Bone Remodeling
MH  - Calcium/metabolism
MH  - Canagliflozin/therapeutic use
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Fractures, Bone/*epidemiology
MH  - Glucosides/therapeutic use
MH  - Humans
MH  - Phosphates/metabolism
MH  - Risk Factors
MH  - Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use
OTO - NOTNLM
OT  - Fracture risk
OT  - Osteoporosis
OT  - SGLT2 inhibitor
OT  - T2DM
EDAT- 2020/07/28 06:00
MHDA- 2021/10/26 06:00
CRDT- 2020/07/26 06:00
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2020/07/26 06:00 [entrez]
AID - 10.1007/s11914-020-00609-z [pii]
AID - 10.1007/s11914-020-00609-z [doi]
PST - ppublish
SO  - Curr Osteoporos Rep. 2020 Oct;18(5):439-448. doi: 10.1007/s11914-020-00609-z.