J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 9, Number 11, November 2017, pages 943-949

Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study

Figures

Figure 1. The column on the right represents the group of hypertensive patients who experienced one or more vertebral fractures during the follow-up. The graph clearly shows that mean age recorded at the entrance into the study was significantly higher (P < 0.001) in hypertensive patients with destructive osteoporosis of the spine, i.e., which developed one or more vertebral fractures (age 81.33 ± 5.27 years) compared with those that did not have vertebral collapses (age 64.53 ± 5.86 years).

Figure 2. The column on the right represents the group of hypertensive patients who experienced one or more vertebral fractures during the follow-up. The chart clearly shows that mean body mass index (BMI) recorded at the entrance into the study was significantly lower (P < 0.001) in hypertensive patients with destructive osteoporosis of the spine, i.e., which developed one or more vertebral fractures (BMI 18.85 ± 1.52) compared with those that did not have vertebral collapses (BMI 24.86 ± 3.10).

Figure 3. In this ROC plot, there is the representation of the very good predictive value (AUC = 0.950) possessed by body mass index (BMI) as a tool for predicting the occurrence of one or more osteoporotic vertebral fractures in hypertensive female patients older than 70 years taking chronic therapy with an oral thiazide diuretic (alone or in combination with another antihypertensive drug). By adopting this method, the best diagnostic accuracy for predicting an osteoporotic spinal fracture has been attributed to the BMI threshold value of 22.4. This means that in the enrolled population of thiazide users, this value is associated to the presence of osteoporotic vertebral collapse or fracture with a sensitivity of 97.9% and a specificity of 81.6% (note on top of the graph).

Tables

**Table 1.** Baseline Demographic Characteristics
	Patients with thiazide-induced hyponatremia (n = 80)	Patients without hyponatremia on thiazide (n = 158)	P-value
Age (years)	74 ± 8.5	65 ± 7.5	< 0.0001
Body mass index (kg/m²)	22.6 ± 4.17	24.19 ± 3.38	0.0017
Duration of follow-up (months)	56.1 ± 10.5	54.8 ± 10.5	0.3705
Ever smoked	23 (28.7%)	48 (30.3%)	0.91
Independent walking ability	50 (62.5%)	128 (81%)	0.0032
Diabetes mellitus	5 (6.25%)	3 (2%)	0.122
Living in long-stay geriatric facility	3 (4%)	11 (7%)	0.394

**Table 2.** Risk of Vertebral Fractures in Thiazide-Induced Hyponatremia (Univariate Analysis)
Hyponatremia found during thiazide	Patients with one or more vertebral fractures
Hyponatremia found during thiazide	Yes	No	Total
This 2 × 2 contingency table shows that, in female hypertensive patients aged 65 or over, taking thiazide diuretics, the odds of experiencing one or more osteoporotic vertebral fractures is significantly (P < 0.0001) higher among patients with hyponatremia (serum sodium level < 135 mEq/L) compared to those with normal serum sodium levels (odds ratio: 7.6025; 95% CI: 3.755 - 15.3923). For further explanations, please see the text.
Yes	34	46	80
No	14	144	158
Total	48	190	238

**Table 3.** Multivariate Logistic Regression Analysis
Variable	Coefficient	Std. error	Odds ratio	95% CI	P
Outcome variable: patients with one or more vertebral fractures. Exposure variables: age (continuous); body mass index (continuous); hyponatremia during thiazide therapy (dichotomous); inability for independent walking (dichotomous); living in geriatric long stay facility (dichotomous); diabetes (dichotomous).
Age (continuous variable)	0.600	0.208	1.823	1.211 - 2.743	0.0039
Body mass index (continuous variable)	-1.852	0.721	0.156	0.038 - 0.645	0.0102
Hyponatremia under thiazide treatment	2.970	1.681	19.508	0.722 - 527.094	0.0773
Inability for independent walking	-3.318	2.289	0.036	0.0004 - 3.216	0.1472
Living in geriatric long stay facility	-3.136	2.482	0.043	0.0003 - 5.630	0.2063