Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002–2012

doi:10.1016/j.bone.2013.09.008

Bone

Volume 57, Issue 2, December 2013, Pages 423-428

https://doi.org/10.1016/j.bone.2013.09.008 Get rights and content

Highlights

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U.S. oral bisphosphonate prescriptions peaked at 31.0 million in 2008 and declined by 53% to 14.7 million in 2012.
•
Sales data were parallel (51% decrease from 2007 through 2012).
•
Intravenous bisphosphonate sales for osteoporosis treatment grew to 561.6 thousand packages in 2010 and declined by 22% in 2012.
•
Decreases coincided with questions about safety and optimal duration, the Fosamax patent expiration, and an economic recession.

Abstract

Bisphosphonates have been widely prescribed to postmenopausal women for treatment and prevention of osteoporosis. Given a background of reports of recent safety problems, questions about optimal duration of use, and the patent expiration of Fosamax in February 2008, we accessed data from pharmaceutical marketing research databases to describe trends in dispensed prescriptions and sales of oral bisphosphonates, characteristics of patients and prescribers, and sales of intravenous bisphosphonates for osteoporosis treatment.

An estimated 21.3 million prescriptions for oral bisphosphonates were dispensed in U.S. retail pharmacies in 2002 that increased 46% to a peak of 31.0 million in 2007 and 2008, and declined by 53% in a four year-period to 14.7 million in 2012. Sales data (number of packages sold in all settings of care) showed parallel trends (66% increase from 2002 through 2007 and 51% decrease from 2007 through 2012). Similarly, intravenous bisphosphonate sales for osteoporosis treatment grew 3.8-fold from 149.5 thousand packages in 2007 to 561.6 thousand in 2010, followed by a 22% decrease in 2012.

Data from an ongoing monthly office-based survey indicated physicians mentioned oral bisphosphonates primarily in visits of older aged Caucasian women with lower body mass for osteoporosis. Frequencies of oral bisphosphonate mentions increased between 2002 and 2012 in visits of Asians and for osteopenia diagnoses.

These data indicate a substantial decline in prescriptions and sales of oral (since 2007–2008) and intravenous (since 2010) bisphosphonates for osteoporosis treatment in the United States. Reasons for, and implications of, the decline should be considered for future research.

Introduction

From the marketing of alendronate (Fosamax), the first oral bisphosphonate drug for treatment of osteoporosis in 1995 that was followed by risedronate (Actonel) in 1998, and ibandronate (Boniva) in 2005 (Table 1), oral bisphosphonate medications have been heavily prescribed to postmenopausal women in the United States. Their popularity is due to their primary indication for the treatment and prevention of osteoporosis, a prevalent condition that increases the risk of hip fracture, immobility, and subsequent mortality primarily in elderly women [1]. Intravenous ibandronic acid (Boniva) approved primarily for osteoporosis treatment became available in 2006 followed by intravenous zoledronic acid (Reclast) in 2007. The Fosamax patent expired in February 2008, generic alendronate became available in 2008, and generic ibandronate, in 2012.

Despite the recognized efficacy of bisphosphonates [2], [3], [4], oral bisphosphonates reportedly have been associated with a number of rare, sometimes controversial adverse events [5] including esophagitis [6], [7], [8] and esophageal cancer [9], [10], and both oral and intravenous formulations have been associated with severe musculoskeletal pain [11], [12], osteonecrosis of the jaw [13], [14], atrial fibrillation [15], [16], and atypical femur fractures [17], [18], [19]. In addition, data are lacking on the optimal duration of therapy in patients with various fracture risks [20], [21], [22]. The current product labeling states that the optimal duration has not been determined and the need for continued therapy should be re-evaluated on a periodic basis [23]. Several of these issues were the focus of a Food and Drug Administration Advisory Committee meeting in September, 2011 [22].

Noting these changes and concerns, we aimed to describe trends in the use of oral and intravenous bisphosphonates in the United States. Our data cover the 11-year period from 2002 through 2012.

Section snippets

Methods

We obtained nationally projected data on the use of oral (alendronate risedronate, and ibandronate) and intravenous (ibandronic acid, zoledronic acid) bisphosphonate drugs approved primarily for osteoporosis treatment and prevention (Table 1) from pharmaceutical marketing research databases purchased and accessed by the Food and Drug Administration from IMS Health and Encuity Research, LLC. Although certain doses of alendronate and risedronate are also indicated for treatment of Paget's disease

Results

An estimated 21.3 million prescriptions for oral bisphosphonates indicated for osteoporosis treatment and prevention were dispensed from U.S. outpatient retail pharmacies in 2002 [24] that increased 46% to a peak 31.0 million in 2007 and 2008 and declined by 53% in a four year-period to 14.7 million in 2012 (Fig. 1). Retail sales accounted for the majority of the market — 64% in 2008 which grew to 67% in 2012, while mail order sales decreased from 26% to 15%, and non-retail sales grew from 10% to

Discussion

Prescriptions for oral bisphosphonates dispensed from U.S. outpatient retail pharmacies climbed to a peak of 31 million in 2007 and 2008 and declined by half during a four-year period to 14.7 million in 2012. Patient-level data mirrored the increase, peak, and decline in prescription data. The number of oral bisphosphonate packages sold experienced a parallel increase through 2007 followed by a 51% decline through 2012. Meanwhile, the number of intravenous packages sold for osteoporosis treatment

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^☆: Disclaimer: The views expressed are those of the authors and may not necessarily represent the official position of the Food and Drug Administration.

^☆☆: Disclosure statement: No conflicts of interest to report.

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Published by Elsevier Inc.

Original Full Length ArticleTrends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002–2012☆,☆☆

Highlights

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Lancet

Gastrointest Endosc

J Oral Maxillofac Surg

J Oral Maxillofac Surg

Epidemiology of osteoporosis and osteoporotic fractures

Epidemiol Rev

Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis

N Engl J Med

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial

JAMA

Osteoporosis treatments and adverse events

Curr Opin Rheumatol

Multiple ulcerative esophagitis caused by alendronate

Am J Gastroenterol

Alendronate-associated esophageal injury: pathologic and endoscopic features

Mod Pathol

Reports of esophageal cancer with oral bisphosphonate use

N Engl J Med

Oral bisphosphonates and risk of cancer of the esophagus, stomach, and colorectum: nested case-control study

BMJ

Alendronate and risedronate: reports of severe bone, joint, and muscle pain

Arch Intern Med

For the HORIZON Recurrent Fracture Trial, zoledronic acid and clinical fractures and mortality after hip fracture

N Engl J Med

Original Full Length Article
Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002–2012☆,☆☆