Economic Burden of Osteoporotic Patients with Fracture: Effect of Treatment With or Without Calcium/Vitamin D Supplements

Figures & data

Table 1 Inclusion/Exclusion Criteria for Cohort Definition and Outcome Measures Considered

Characteristic	Disease and Drug Codes
Inclusion Criteria
Patient/disease characteristics
Vertebral fractures, with/without spinal cord injury	ICD-9-CM codes 805 and 806
Hip fractures	ICD-9-CM code 820
Subjects discharged for hip fractures associated with a concomitant surgical procedure	ICD-9-CM codes 79.00, 79.05, 79.10, 79.15, 79.20, 79.25, 79.30, 79.35, 79.40, 79.45, 79.50, 79.55; 81.51, 81.52
One hospitalization discharge diagnosis of osteoporosis	ICD-9-CM code 733.0
Anti-fracture drugs
Bisphosphonates^*	ATC M05BA, excluding M05BA08
Plus vitamin D	ATC M05BB03
Plus denosumab and strontium ranelate	ATC M05BX
Plus teriparatide and parathyroid hormones	H05AA
Plus calcitonin	H05BA
Plus selective estrogen receptor modulators	G03XC
Calcium and vitamin D	ATC codes A12AA, A12AX, A11CC (excluding A11CC03 and A11CC04)
Exclusion criteria
Renal disease	ICD-9-CM codes 584–585 or exemption code 023
Malignancies	ICD-9-CM codes 140–208 or exemption code 048
Follow-up variables
Drugs
Corticosteroids for systemic use	ATC H02
Platelet aggregation inhibitors	ATC B01AC
Vitamin K antagonists/Xa factor inhibitors	ATC B01AA, B01AE, B01AF
Analgesics	ATC N02
Anticonvulsants	ATC N03
Antipsychotics/anxiolytics	ATC N05A, N05B
Proton pump inhibitors	ATC A02BA
Incidence of re-fracture
Vertebral forms with and without spinal cord injury	ICD-9-CM codes 805, 806
Radius and ulna and hip fractures	ICD-9-CM codes 813 and 820
With concomitant replacement procedure	79.00, 79.05, 79.10, 79.15, 79.20, 79.25, 79.30, 79.35, 79.40, 79.45, 79.50, 79.55, 81.51, 81.52

Notes:

* Bisphosphonates were the only anti-fracture drug that could have been administered together with vitamin D as a single tablet. All other drugs were administered separately as different tablets.

Abbreviations: ATC, Anatomical Therapeutic Chemical; ICD, International Classification of Diseases.

Table 2 Baseline Characteristics of the Study Population According to the Treatment Prescribed

	Untreated Cohort (N=1443)	Treated Cohort (N=2032)	p-value	Treated Cohort		p-value
				Osteoporosis Drug Only (N=333)	Osteoporosis Drug + Ca/VitD (N=1699)
Age, years mean (±SD)	83.6 (8.7)	78.2 (8.7)	<0.001	81.3 (±8.0)	77.6 (±8.7)	<0.001
Female, %	83.0	94.1	<0.001	91.6	94.6	0.034
CCI score, %
≤ 1	71.7	72.2	0.704	70.0	72.7	0.311
> 1	28.3	27.8		30.0	27.3
Comorbidities, %
Hypertension	75.1	71.0	0.008	75.4	70.2	0.055
Diabetes	18.4	13.4	<0.001	15.3	13.0	0.258
Dyslipidemia	23.1	24.9	0.228	21.6	25.5	0.136
Ischemic heart failure	4.6	2.8	0.003	2.4	2.8	0.667
Cardiac dysrhythmias	11.5	8.8	0.009	11.4	8.3	0.067
Heart failure	3.4	1.5	<0.001	2.4	1.3	0.125
Stroke	6.5	3.2	<0.001	4.2	3.1	0.282
COPD	13.4	12.3	0.321	12.3	12.3	0.996
Previous osteoporosis treatment, %
Osteoporosis drugs	36.8	70.4	<0.001	84.4	67.7	<0.001
Calcium/Vitamin D	78.3	75.4	0.045	45.3	81.3	<0.001
Other drugs, %
Corticosteroids for systemic use	10.5	17.0	<0.001	12.0	18.0	0.008
Platelet aggregation inhibitors	40.3	34.0	<0.001	36.9	33.4	0.209
Vitamin K antagonists/Xa factor inhibitors	10.6	6.4	<0.001	9.0	5.9	0.033
Analgesics	14.0	15.7	0.167	12.0	16.4	0.043
Anticonvulsants	6.3	7.5	0.181	7.5	7.5	0.984
Antipsychotics/anxiolytics	6.7	3.2	<0.001	4.5	3.0	0.157
PPI	48.9	52.0	0.066	48.9	52.6	0.220

Abbreviations: SD, Standard Deviation; CCI, Charlson Comorbidity Index; COPD, Chronic Obstructive Pulmonary Disease; PPI, Proton Pump Inhibitor.

Figure 1 Patient disposition.

Table 3 Mean Annual Healthcare Cost (Excluding Costs Related to Index Hospitalization) per Patients Over the Follow-Up Period

Cost Items	Untreated Cohort (N=1443)	Treated Cohort (N=2032)	p-value	Treated Cohort
				Osteoporosis Drug Only (N=333)	Osteoporosis Drug + Ca/VitD (N=1699)	p-value
Drugs (mean ± SD) Median Min-max	677.18 (±1,322.65) 319.44 0.00–37,227.00	1,159.55 (±1,585.58) 760.795 0.00–28,720.70	<0.001	1,056.95 (±1,386.44) 727.45 0.00–14,588.25	1,179.66 (±1,621.36) 766.04 15.44–28,720.70	0.196
Hospitalizations (mean ± SD) Median Min-max	7,801.74 (±25,380.60) 1,431.58 0.00–657,400.00	2,627.77 (±6,212.82) 806.37 0.00–128,988.80	<0.001	4,407.92 (±10,615.14) 1,114.43 0.00–128,988.80	2,278.86 (±4,836.70) 783.25 0.00–69,271.51	<0.001
Outpatient services (mean ± SD) Median Min-max	810.93 (±4,601.38) 176.55 0.00–124,456.10	640.94 (±1,253.65) 281.28 0.00–21,376.61	0.113	512.01 (±1084.37) 178.97 0.00–9991.07	666.21 (±1282.99) 305.23 0.00–21,376.61	0.040
Total (mean ± SD) Median Min-max	9,289.85 (±25,846.20) 2,713.52 0.00–657,400.00	4,428.26 (±6,770.90) 2,568.50 29.66–132,152.40	<0.001	5,976.88 (±10,993.06) 2,506.35 29.66–132,152.40	4,124.74 (±5,535.78) 2,571.33 32.88–70,004.80	<0.001

Note: Values expressed in Euro.

Abbreviation: SD, standard deviation.

Table 4 Multivariate Analysis of Total Healthcare Cost, Excluding Costs Related to Hospitalization Index

	β	95% CI		p-value
Age	33.66	5.13	62.19	0.021
Gender	877.35	–291.57	2046.27	0.141
CCI score >1	442.22	–203.32	1087.76	0.179
Comorbidities
Hypertension	92.04	–431.93	616.02	0.731
Diabetes	585.09	–339.29	1509.46	0.215
Dyslipidemia	165.12	–457.74	787.97	0.603
Ischemic heart failure	1446.58	–1133.00	4026.16	0.272
Cardiac dysrhythmias	837.32	–409.88	2084.53	0.188
Heart failure	1385.83	–2310.40	5082.06	0.462
Stroke	1486.30	–851.96	3824.57	0.213
COPD	633.28	–215.27	1481.83	0.144
Other drugs
Corticosteroids for systemic use	174.88	–587.05	936.81	0.653
Platelet aggregation inhibitors	248.20	–344.83	841.22	0.412
Vitamin K antagonists/Xa factor inhibitors	1857.97	147.27	3568.67	0.033
Analgesics	1364.62	422.57	2306.67	0.005
Anticonvulsants	918.01	–210.56	2046.58	0.111
Antipsychotics/anxiolytics	1566.89	–366.80	3500.57	0.112
PPI	419.11	–104.70	942.92	0.117
MPR
<40%	Reference
≥40% <80%	–245.29	–896.57	405.99	0.460
≥80%	–122.35	–669.74	425.04	0.661
Type of treatment
Osteo only [Reference]^*	Reference
Osteo and Ca/VitD	–1296.91	–2155.90	–437.93	0.003

Note:

* “Osteo only” refers to osteoporosis drugs only.

Abbreviations: CCI, Charlson Comorbidity Index; CI, confidence interval; COPD, Chronic Obstructive Pulmonary Disease; MPR, Medication Possession Ratio; PPI, Proton Pump Inhibitor.