Cardioprotective Effect of Oral Bisphosphonates

4 Mar, 22

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Introduction

Osteoporosis or low bone mass does not exist in isolation, but often co-exists with other chronic diseases, particularly cardiovascular [CV]. Awareness of the need for management of CV risk factors alongside fracture risk is growing, given multiple reports of increased CV mortality following osteoporotic fragility fracture.

Aim

To determine the risk of incident CV disease associated with oral bisphosphonate (oBP) use in oral BP (oBP) users and non-users

Patient Profile

Individuals aged ≥45 years referred for bone mineral density (BMD) testing
Individuals were considered exposed (oBP user) if they filled at least one prescription for an oBP (representing new users) from 1 January 2003 to 31 December 2014 had a real BMD (hip and spine) determined by DXA within two years of the prescription

Methods

Cohort study
5,643 oBP users (4564 women; 80.9%) and 21,879 non-users (16730 women; 76.5%) with clinical indication for BMD assessment

Alendronate accounted for 96% of oBP prescriptions were included in analysis

Study Outcomes

Hospitalization for any CV event
Secondary study outcomes were specific CV events. Negative (inguinal hernia surgery and ingrown toenail) and positive (fragility fracture) control outcomes assessed systemic bias

Results

For the primary outcome, there were 406 (15.8%) events in oBP users [rate = 73.48 (66.67 to 80.98)] and 837 (18.3%) in non-users [rate=104.73 (97.87 to 112.07)]
oBP use was associated with a 26% reduced risk of CV events

Figure 1: Incidence rates for the primary study outcome [hospitalization for any CV event]

oBP use was only associated reduced risk of CV or all-cause mortality

Table 1: Effects estimates [Hazard ratios] in the propensity-score matched sub-cohorts analysed on an intention-to-treat and per-protocol basis

Analysis	Intention-to-treat			Per-protocol
Adjustments	oBP	oBP & Pscore	oBP & Pscore & Unbalanced covariates	oBP	oBP & Pscore	oBP & Pscore & Unbalanced covariates


Hospitalisation outcomes
Any CVD event	0.74	0.68	0.67	0.90	0.84	0.82
Atrial fibrillation	0.67	0.60	0.63	0.79	0.71	0.74
Cardiac arrhythmia	0.61	0.61	0.66	0.80	0.80]	0.89
Myocardial infarction	0.92	0.86	0.90	1.04	0.98	1.03
Heart failure	0.76	0.68	0.65	0.97	0.90	0.84
Stroke	0.60	0.56	0.46	0.82	0.76	0.61
Ischaemic stroke	0.64	0.60	0.50	0.86	0.81	0.66
Atherosclerotic	0.45	0.42	0.35	0.63	0.59	0.51
Aneurysm	0.55	0.53	0.57	0.72	0.69	0.75
Peripheral artery disease	0.73	0.71	0.65	0.95	0.92	0.88
Mortality outcomes
Any CVD death	0.55	0.48	0.50	0.44	0.36	0.37
Stroke death	0.45	0.37	0.37	0.39	0.33	0.45
Myocardial infarction	0.64	0.56	0.53	0.67	0.52	0.47
All-cause	0.59	0.45	0.35	0.38	0.28	0.23

Unbalanced covariates: lumbar spine BMD, osteoporosis in the spine, prior fracture at any site. Pscore = propensity score

Effect of oBP use on Osteoporotic Fractures

There were 247 (9.6%) fractures in oBP users and 630 (13.8%) fractures in propensity score-matched non- users with an adjusted HR of 0.26
Oral BP use was associated with an anticipated reduction in fracture rate, but was not associated with inguinal hernia repair or ingrown toenails

Conclusion

There was a reduced risk of CV events in the cohort of Danish oral BP users matched on a clinical indication for DXA to non-users
The data supports findings from BP RCTs showing a reduction in CV events
Additional adjustment for BMD did not alter outcomes, which questions the prognostic value of BMD on CV risk in the setting of osteoporosis

Reference

J Clin Endocrinol Metab.2020 ;105(10):dgaa481