Gastrointestinal events and association with initiation of treatment for osteoporosis

Figures & data

Figure 1 Patient selection.

Table 1 Patient characteristics in the pre-index perioda

	All patients (n=65,344)	Without pre-index GI event (n=47,516)	With pre-index GI event (n=17,828)	P-valueb
Pre-index GI event	17,828 (27.3)	–	17,828 (27.3)
Age (years), mean (SD)	65.7 (8.9)	65.5 (8.8)	66.2 (9.1)	<0.001
55–64	37,201 (56.9)	27,432 (57.7)	9,769 (54.8)	–
65–74	14,148 (21.7)	10,296 (21.7)	3,852 (21.6)	–
75–84	12,837 (19.7)	9,044 (19.0)	3,793 (21.3)	–
85+	1,158 (1.8)	744 (1.6)	414 (2.3)	–
Medication use
Gastroprotective agents	10,185 (15.6)	3,444 (7.3)	6,741 (37.8)	<0.001
NSAIDs	14,103 (21.6)	9,399 (19.8)	4,704 (26.4)	<0.001
Glucocorticoids	8,917 (13.7)	5,570 (11.7)	3,347 (18.8)	<0.001
CCI score, mean (SD)	0.65 (1.12)	0.52 (0.96)	1.01 (1.41)	<0.001
Comorbidities
Chronic inflammatory bowel disease	468 (0.7)	199 (0.4)	269 (1.5)	<0.001
Chronic inflammatory joint disease	13,922 (21.3)	8,817 (18.6)	5,105 (28.6)	<0.001
Celiac disease	223 (0.3)	88 (0.2)	135 (0.8)	<0.001
Diabetes	9,211 (14.1)	6,094 (12.8)	3,117 (17.5)	<0.001
Depression	3,759 (5.8)	2,106 (4.4)	1,653 (9.3)	<0.001
Chronic kidney disease	882 (1.4)	451 (1.0)	431 (2.4)	<0.001
Hypertension	31,447 (48.1)	21,164 (44.5)	10,283 (57.7)	<0.001
GI mucositis and urination problems	4,830 (7.4)	2,623 (5.5)	2,207 (12.4)	<0.001
Hyperparathyroidism	366 (0.6)	219 (0.5)	147 (0.8)	<0.001
Vitamin D deficiency	365 (0.6)	219 (0.5)	146 (0.8)	<0.001
Fatigue	10,712 (16.4)	6,469 (13.6)	4,243 (23.8)	<0.001
Fractures
Any	4,476 (6.9)	2,867 (6.0)	1,609 (9.0)	<0.001
Hip	991 (1.5)	604 (1.3)	387 (2.2)	<0.001
Vertebral	1,256 (1.9)	688 (1.5)	568 (3.2)	<0.001
Non-vertebral	2,864 (4.4)	1,918 (4.0)	946 (5.3)	<0.001

Notes:

a Values are presented as n (%) unless otherwise indicated;

b P-values are for the comparison between patients with and without a pre-index GI diagnosis.

Abbreviations: CCI, Charlson Comorbidity Index; GI, gastrointestinal; SD, standard deviation; NSAID, nonsteroidal anti-inflammatory drug.

Figure 2 Treatment with medications for osteoporosis in the post-index period by (A) pre-index GI events and (B) post-index GI events.

Note: ^aComparison of treatment pattern distribution among patients with and without GI events.
Abbreviation: GI, gastrointestinal.

Table 2 Distribution of GI events in the pre-index and post-index periods

Pre-index period	Post-index period		Total
	No GI events	GI events
No GI events	39,800 (83.8%)	7,716 (16.2%)	47,516 (72.7%)
GI events	10,090 (56.6%)	7,738 (43.4%)	17,828 (27.3%)
Total	49,890 (76.3%)	15,454 (23.7%)	65,344

Abbreviation: GI, gastrointestinal.

Table 3 Time-varying Cox regression model for the association between post-index GI events and any osteoporosis treatment (bisphosphonate or non-bisphosphonate) initiation

Independent variable	Hazard ratio	95% CI	P-value
Post-index GI events	0.25	(0.24–0.26)	<0.0001
Age group, years			0.081
65–74 versus 55–64	1.01	(0.98–1.05)
75–84 versus 55–64	1.00	(0.96–1.03)
85+ versus 55–64	0.87	(0.78–0.98)
Pre-index medication use
Gastroprotective agents	1.46	(1.41–1.52)	<0.0001
NSAIDs	1.20	(1.16–1.24)	<0.0001
Corticosteroids	1.18	(1.13–1.22)	<0.0001
Charlson comorbidity index score	1.01	(0.99–1.03)	0.191
Comorbidity
Chronic inflammatory bowel disease	1.08	(0.93–1.26)	0.309
Chronic inflammatory joint disease	0.86	(0.83–0.89)	<0.0001
Celiac disease	1.08	(0.88–1.36)	0.420
Diabetes	0.80	(0.77–0.84)	<0.0001
Depression	1.06	(1.00–1.12)	0.044
Chronic kidney disease	1.02	(0.89–1.16)	0.780
Hypertension	0.88	(0.85–0.90)	<0.0001
GI mucositis and urination problems	0.97	(0.92–1.02)	0.282
Hyperparathyroidism	0.97	(0.81–1.17)	0.767
Vitamin D deficiency	0.91	(0.76–1.08)	0.279
Fatigue	1.00	(0.96–1.03)	0.851

Abbreviations: CI, confidence interval; GI, gastrointestinal; NSAIDs, nonsteroidal anti-inflammatory drugs.

Table 4 Discrete choice model examining the association between post-index GI events and receipt of bisphosphonate among patients who initiated osteoporosis treatment

Independent variable (reference: non-bisphosphonate initiation)	Odds ratio	95% CI	P-value
Pre-index GI events	0.85	(0.78–0.94)	0.001
Post-index GI events	0.61	(0.54–0.68)	<0.0001
Age group, years
65–74 versus 55–64	0.96	(0.87–1.06)	0.442
75–84 versus 55–64	0.79	(0.71–0.87)	<0.0001
85+ versus 55–64	0.72	(0.54–0.97)	0.029
Pre-index medication use
Gastroprotective agents	0.68	(0.62–0.76)	<0.0001
NSAIDs	1.07	(0.97–1.17)	0.184
Corticosteroids	0.98	(0.88–1.09)	0.733
Charlson comorbidity index score	0.96	(0.92–1.01)	0.096
Comorbidity
Chronic inflammatory bowel disease	0.99	(0.65–1.51)	0.953
Chronic inflammatory joint disease	1.05	(0.95–1.17)	0.320
Celiac disease	0.72	(0.41–1.26)	0.248
Diabetes	1.22	(1.05–1.41)	0.009
Depression	1.11	(0.94–1.31)	0.232
Chronic kidney disease	0.90	(0.64–1.28)	0.565
Hypertension	1.06	(0.97–1.15)	0.195
GI mucositis and urination problems	0.86	(0.75–0.99)	0.040
Hyperparathyroidism	1.14	(0.66–1.98)	0.635
Vitamin D deficiency	1.19	(0.68–2.10)	0.540
Fatigue	1.04	(0.93–1.16)	0.474

Abbreviations: CI, confidence interval; GI, gastrointestinal; NSAIDs, nonsteroidal anti-inflammatory drugs.

Table S1 Codes used to identify gastrointestinal events, fractures, and use of bisphosphonates and non-bisphosphonates

	Code	Description
GI events
ICD-9-CM	456.0	Esophageal varices with hemorrhage
	456.1	Esophageal varices without hemorrhage
	530.xx	Diseases of esophagus
	531.xx	Gastric ulcer
	532.xx	Duodenal ulcer
	533.xx	Peptic ulcer, site NOS
	534.0-3	Gastrojejunal ulcer
	535.xx	Gastritis and duodenitis
	536.2	Persistent vomiting
	536.8	Dyspepsia and other specified disorders of function of stomach
	536.9	Stomach function disorders NOS
	537.4	Gastric/duodenal fistula
	537.8x	Gastroduodenal disorders NEC
	537.9	Gastroduodenal disorders NOS
	569.83	Perforation of intestine
	578.xx	GI hemorrhage
	787.0x	Nausea and vomiting
	787.1	Heartburn
	787.2	Dysphagia
	789.0x	Abdominal pain
	792.1	Abnormal stool/occult blood
	793.4	Abnormal exam GI tract
CPT	43200	Endoscopy, rigid or flexible; diagnostic, with or without collection of specimen(s) by brushing or washing (separate procedure)
	43202	Esophagoscopy, rigid or flexible; diagnostic, with or without collection of specimen(s) by brushing or washing (separate procedure) with biopsy, single or multiple
	43227	Esophagoscopy, rigid or flexible; diagnostic, with or without collection of specimen(s) by brushing or washing (separate procedure) with control of bleeding, any method
	43235	Endoscopy, rigid or flexible; diagnostic, with or without collection of specimen(s) by brushing or washing (separate procedure)
	43239	Upper GI endoscopy including esophagus, stomach, and either the duodenum and/or jejunum as appropriate; diagnostic with or without collection of specimen(s) by brushing or washing (separate procedure) with biopsy, single or multiple
	43255	Upper GI endoscopy including esophagus, stomach, and either the duodenum and/or jejunum as appropriate; diagnostic with or without collection of specimen(s) by brushing or washing (separate procedure), with control of bleeding, any method
	44602	Suture of small intestine (enterorrhaphy) for perforated ulcer
	44603	Suture of small intestine (enterorrhaphy) for perforated ulcer
	44605	Suture of large intestine (colorrhaphy) for perforated ulcer
	74240	Radiologic examination, GI tract, upper; with or without delayed film, without KUB
	74241	Radiologic examination, GI tract, upper; with or without delayed films, with KUB
	74245	Radiologic examination, GI tract, upper; with small bowel, includes multiple serial films
	74246	Radiologic examination, GI tract, upper, air contrast, with specific high density barium, effervescent agent, with or without glycagon; with or without delayed films, with KUB
	74247	Radiologic examination, GI tract, upper, air contrast, with specific high density barium, effervescent agent, with or without glycagon; with or without delayed films, without KUB
	74249	Radiologic examination, GI tract, upper, air contrast, with specific high density barium, effervescent agent, with or without glycagon; with small bowel follow-through

Abbreviations: CPT, Current Procedural Terminology; GI, gastrointestinal; ICD-9-CM Dx, International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes; KUB, kidney, ureter, and bladder X-ray; NEC, not elsewhere classifiable; NOS, not otherwise specified.