Undertreatment of osteoporosis and the role of gastrointestinal events among elderly osteoporotic women with Medicare Part D drug coverage

Figures & data

Table 1 OP treatment patterns after diagnosis

Treatment pattern	N (%)
All patients	126,188 (100)
No OP treatment within 1 year of OP diagnosis	91,021 (72.1)
First OP treatment within 1 year of OP diagnosis
Bisphosphonate	27,267 (21.6)
Alendronate	15,194 (12.0)
Ibandronate	4,702 (3.7)
Risedronate	6,144 (4.9)
Zoledronic acid	1,227 (1.0)
Nonbisphosphonate	7,900 (6.3)
Calcitonin	5,438 (4.3)
Raloxifene	1,317 (1.0)
Teriparatide	1,145 (0.9)
Average time from OP diagnosis to treatment initiation, days	Mean (SD)
Any treatment (N=35,167)	75.4 (88.9)
Bisphosphonate (N=27,267)	79.4 (91.8)
Nonbisphosphonate (N=7,900)	61.6 (76.3)

Abbreviations: OP, osteoporosis; SD, standard deviation; N, total number.

Figure 1 Identification of the study cohort.

Abbreviations: N, total number; OP, osteoporosis.

Table 2 Baseline patient characteristics for all patients and by postindex OP treatment status

Characteristic	All patients(N=126,188)	Treatment status			BIS treatment status among those being treated
		No treatment (N=91,021)	Initiated any treatment (N=35,167)	P-value	Initiated BIS treatment (N=27,267)	Initiated non-BIS treatment (N=7,900)	P-value
Age, mean (SD)	78.5 (7.9)	78.7 (8.0)	77.9 (7.4)	<0.0001	77.2 (7.1)	80.2 (8.1)	<0.0001
Age distribution, N (%)				<0.0001			<0.0001
66–74 years	43,156 (34.2)	30,662 (33.7)	12,494 (35.5)		10,393 (38.1)	2,101 (26.6)
75–84 years	50,882 (40.3)	36,010 (39.6)	14,872 (42.3)		11,696 (42.9)	3,176 (40.2)
>85 years	32,150 (25.5)	24,349 (26.8)	7,801 (22.2)		5,178 (19.0)	2,623 (33.2)
Dual eligibility,a N (%)	23,606 (18.7)	16,416 (18.0)	7,190 (20.5)	<0.0001	5,250 (19.3)	1,940 (24.6)	<0.0001
Charlson comorbidity index, mean (SD)	1.53 (1.60)	1.57 (1.63)	1.42 (1.52)	<0.0001	1.35 (1.47)	1.64 (1.63)	<0.0001
Common OP-related comorbidities, N (%)
Chronic inflammatory bowel disease	1,080 (0.9)	771 (0.9)	309 (0.9)	0.58	238 (0.9)	71 (0.9)	0.83
Chronic inflammatory joint disease	74,323 (58.9)	54,159 (59.6)	20,164 (57.3)	<0.0001	15,326 (56.2)	4,838 (61.2)	<0.0001
Celiac disease	206 (0.2)	141 (0.2)	65 (0.2)	0.24	40 (0.2)	25 (0.3)	0.002
Diabetes (type 1 or 2)	36,565 (29.0)	27,159 (29.8)	9,406 (26.8)	<0.0001	7,387 (27.1)	2,019 (25.6)	0.007
Chronic kidney disease	13,399 (10.6)	10,029 (11.0)	3,370 (9.6)	<0.0001	2,433 (8.9)	937 (11.9)	<0.0001
Hypertension	96,178 (76.2)	69,802 (76.7)	26,376 (75.0)	<0.0001	20,467 (75.1)	5,909 (74.8)	0.63
Hyperparathyroidism	1,224 (1.0)	902 (1.0)	322 (0.9)	0.22	245 (0.9)	77 (1.0)	0.53
Vitamin D deficiency	1,934 (1.5)	1,450 (1.6)	484 (1.4)	0.01	366 (1.3)	118 (1.5)	0.31
OP-related fractures, N (%)
Any fracture	15,231 (12.1)	10,263 (11.3)	4,968 (14.1)	<0.0001	3,514 (12.9)	1,454 (18.4)	<0.0001
Hip	4,278 (3.4)	3,014 (3.3)	1,264 (3.6)	0.01	894 (3.3)	370 (4.7)	<0.0001
Vertebral	5,367 (4.3)	3,354 (3.7)	2,013 (5.7)	<0.0001	1,287 (4.7)	726 (9.2)	<0.0001
Nonvertebral	8,542 (6.8)	5,915 (6.5)	2,627 (7.5)	<0.0001	1,966 (7.2)	661 (8.4)	0.001
GI-related drug use, N (%)
Glucocorticoids	25,601 (20.3)	18,000 (19.8)	7,601 (21.6)	<0.0001	5,811 (21.3)	1,790 (22.7)	0.01
NSAIDs	30,251 (24.0)	21,237 (23.3)	9,014 (25.6)	<0.0001	7,176 (26.3)	1,838 (23.3)	<0.0001
Gastroprotective agents
Any agent	40,748 (32.3)	28,779 (31.6)	11,969 (34.0)	<0.0001	8,495 (31.2)	3,474 (44.0)	<0.0001
Proton pump inhibitors	34,055 (27.0)	23,919 (26.3)	10,136 (28.2)	<0.0001	7,163 (26.3)	2,973 (37.6)	<0.0001
H2 antagonist	8,881 (7.0)	6,367 (7.0)	2,514 (7.2)	0.34	1,800 (6.6)	714 (9.0)	<0.0001
Cytoprotectants	2,461 (2.0)	1,730 (1.9)	731 (2.1)	0.04	482 (1.8)	249 (3.2)	<0.0001
Total pill burden,b mean (SD)	7.8 (5.7)	7.79 (5.71)	7.83 (5.64)	0.07	7.53 (5.52)	8.85 (5.93)	<0.0001
Total annual health care costs, mean USD (SD)	24,999 (54,394)	25,595 (55,954)	23,456 (50,101)	0.60	21,885 (47,736)	28,882 (57,193)	<0.0001

Notes:

a Eligible for Medicaid and Medicare;

b count of distinct oral drug molecules in the baseline period.

Abbreviations: OP, osteoporosis; BIS, bisphosphonates; N, total number; SD, standard deviation; GI, gastrointestinal; NSAIDs, nonsteroidal anti-inflammatory drugs.

Table 3 Distribution of patients by GI events before and after OP diagnosis

Cohort	Pre-OP diagnosis of GI events, N (%)	Post-OP diagnosis GI events, N (%)		Total
		No	Yes
All patients (N=126,188)	No	61,100 (82.9)	12,577 (17.1)	73,677 (58.4)
	Yes	29,831 (56.8)	22,680 (43.2)	52,511 (41.6)
	Total	90,931 (72.1)	35,257 (27.9)	126,188 (100.0)
Patients who did not initiate	No	35,767 (67.2)	17,497 (32.9)	53,264 (58.5)
OP treatment (N=91,021)	Yes	11,614 (30.8)	26,143 (69.2)	37,757 (41.5)
	Total	47,381 (52.1)	43,640 (47.9)	91,021 (100.0)
Patients initiated on BIS (N=27,267)	No	14,558 (89.0)	1,803 (11.0)	16,361 (60.0)
	Yes	7,554 (69.3)	3,352 (30.7)	10,906 (40.0)
	Total	22,112 (81.1)	5,155 (18.9)	27,267 (100.0)
Patients initiated on non-BIS (N=7,900)	No	3,389 (83.6)	663 (16.4)	4,052 (51.3)
	Yes	2,379 (61.8)	1,469 (38.2)	3,848 (48.7)
	Total	5,768 (73.0)	2,132 (27.0)	7,900 (100.0)

Abbreviations: GI, gastrointestinal; OP, osteoporosis; N, total number; BIS, bisphosphonates.

Table 4 Logistic regression analysis of the association of postdiagnosis GI events and OP treatment initiation

Independent variable	OP treatment initiation Any OP treatment versus no OP treatment
	Odds ratioa	95% CI		P-value
Presence of postdiagnosis GI event (ref: absence of postdiagnosis GI events)
Patients without a prediagnosis GI event	0.243	0.232	0.254	<0.0001
Patients with a prediagnosis GI event	0.260	0.250	0.270	<0.0001
Baseline characteristics
Age at diagnosis, years (ref: 66–74 years)
75–84 years	1.142	1.108	1.177	<0.0001
≥85 years	1.097	1.057	1.138	<0.0001
Pill burden	1.014	1.011	1.018	<0.0001
Medication use
Gastroprotective agents	1.577	1.527	1.628	<0.0001
Glucocorticoids	1.078	1.044	1.113	<0.0001
NSAID	1.122	1.085	1.161	<0.0001
Dual eligibility (yes)	1.379	1.333	1.427	<0.0001
Baseline bone mineral density testing (yes)	2.097	2.040	2.156	<0.0001
Charlson comorbidity index	0.988	0.975	1.000	0.059
OP-related comorbidities
Chronic inflammatory bowel disease	1.082	0.940	1.246	0.273
Chronic inflammatory joint disease	0.996	0.968	1.025	0.795
Celiac disease	1.247	0.911	1.707	0.167
Diabetes	0.817	0.789	0.847	<0.0001
Chronic kidney disease	0.949	0.904	0.996	0.034
Hypertension	0.900	0.872	0.930	<0.0001
Hyperparathyroidism	0.918	0.801	1.051	0.215
Vitamin D deficiency	0.869	0.779	0.970	0.012
12-month preindex health care costs	1.001	1.000	1.001	<0.001

Note:

a Adjusted for patient baseline characteristics.

Abbreviations: GI, gastrointestinal; OP, osteoporosis; CI, confidence interval; ref, reference group; NSAID, nonsteroidal anti-inflammatory drug.

Table 5 Logistic regression of the association of postdiagnosis GI events and the type of treatment initiated among those patients who initiated treatment

Independent variable	Bisphosphonate treatment initiation Bisphosphonate versus nonbisphosphonate
	Odds ratioa	95% CI		P-value
Presence of postdiagnosis GI event (ref: absence of postdiagnosis GI events)
Patients without a prediagnosis GI event	0.887	0.804	0.979	0.0171
Patients with a prediagnosis GI event	0.859	0.797	0.926	<0.0001
Baseline characteristics
Age at diagnosis (ref: 66–74 years)
75–84 years	0.801	0.752	0.854	<0.0001
≥85 years	0.521	0.485	0.559	<0.0001
Pill burden	0.970	0.964	0.976	<0.0001
Medication use
Gastroprotective agents	0.682	0.642	0.724	<0.0001
Glucocorticoids	1.291	1.211	1.377	<0.0001
NSAID	1.102	1.031	1.178	0.0043
Dual eligibility (yes)	0.818	0.767	0.871	<0.0001
Baseline bone mineral density testing (yes) in 6 months before the OP diagnosis	2.446	2.318	2.581	<0.0001
Charlson comorbidity index	0.956	0.933	0.981	0.0005
OP-related comorbidities
Chronic inflammatory bowel disease	1.030	0.779	1.360	0.8369
Chronic inflammatory joint disease	0.966	0.912	1.024	0.2453
Celiac disease	0.461	0.273	0.780	0.0039
Diabetes	1.285	1.195	1.381	<0.0001
Chronic kidney disease	0.933	0.850	1.023	0.1390
Hypertension	1.227	1.151	1.309	<0.0001
Hyperparathyroidism	0.914	0.697	1.198	0.5137
Vitamin D deficiency	0.881	0.707	1.097	0.2562
12-month health care costs	1.000	0.999	1.000	0.8289

Note:

a Adjusted for patient baseline characteristics.

Abbreviations: GI, gastrointestinal; CI, confidence interval; ref, reference group; NSAID, nonsteroidal anti-inflammatory drug; OP, osteoporosis.

Table S1 Codes for the identification of gastrointestinal events

	Description
ICD-9-CM code
456.0	Esophageal varices with hemorrhage
456.1	Esophageal varices without hemorrhage
530.0x	Achalasia and cardiospasm
530.1x	Esophagitis
530.2	Ulcer of esophagus
530.2	Ulcer of esophagus without bleeding
530.21	Ulcer of esophagus with bleeding
530.3	Stricture of esophagus
530.4	Perforation of esophagus
530.5	Dyskinesia of esophagus
530.7	Mallory–Weiss syndrome
530.81	Esophageal reflux (GERD)
530.82	Esophageal hemorrhage
530.84	Tracheoesophageal fistula
530.89	Other disorders of the esophagus
531.xx	Gastric ulcer
531	Gastric ulcer, acute with hemorrhage
531.1	Gastric ulcer, acute with perforation
531.2	Gastric ulcer, acute with hemorrhage and perforation
531.3	Gastric ulcer, acute without hemorrhage or perforation
531.4	Gastric ulcer, chronic or unspecified with hemorrhage
531.5	Gastric ulcer, chronic or unspecified with perforation
531.6	Gastric ulcer, chronic or unspecified with hemorrhage and perforation
531.7	Gastric ulcer, chronic without hemorrhage or perforation
531.9	Gastric ulcer, unspecified as acute or chronic, without hemorrhage or perforation
532.xx	Duodenal ulcer
532	Duodenal ulcer, acute with perforation
532.1	Duodenal ulcer, acute with hemorrhage
532.2	Duodenal ulcer, acute with hemorrhage and perforation
532.3	Duodenal ulcer, acute without hemorrhage or perforation
532.4	Duodenal ulcer, chronic or unspecified with hemorrhage
532.5	Duodenal ulcer, chronic or unspecified with perforation
532.6	Duodenal ulcer, chronic or unspecified with hemorrhage and perforation
532.7	Duodenal ulcer, chronic without hemorrhage or perforation
532.9	Duodenal ulcer, unspecified as acute or chronic, without hemorrhage or perforation
533.xx	Peptic ulcer, site NOS
533	Peptic ulcer, acute with hemorrhage
533.1	Peptic ulcer, acute with perforation
533.2	Peptic ulcer, acute with perforation and hemorrhage
533.3	Peptic ulcer, acute without hemorrhage or perforation
533.4	Peptic ulcer, chronic or unspecified with hemorrhage
533.5	Peptic ulcer, chronic or unspecified with perforation
533.6	Peptic ulcer, chronic or unspecified with hemorrhage and perforation
533.7	Peptic ulcer, chronic without hemorrhage or perforation
533.9	Peptic ulcer, unspecified as acute or chronic, without hemorrhage or perforation
534	Gastrojejunal ulcer
534.1	Gastrojejunal ulcer
534.2	Gastrojejunal ulcer
534.3	Gastrojejunal ulcer
535.0x	Acute gastritis
535.11	Atrophic gastritis with hemorrhage
535.21	Gastric mucosal hypertrophy with hemorrhage
535.4x	Gastritis NEC
535.5x	Gastritis/duodenitis NOS
535.6x	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-4 code
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: ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; GERD, gastroesophageal reflux disease; NOS, not otherwise specified; NEC, not elsewhere classifiable; GI, gastrointestinal; CPT, Current Procedural Terminology; KUB, kidney, ureter, and bladder X-ray.