Bone formation markers in patients with glucocorticoid-induced osteoporosis
treated with teriparatide or alendronate
☆
Richard Eastell
a,
⁎
, Peiqi Chen
b
, Kenneth G. Saag
c
, Alan L. Burshell
d
, Mayme Wong
b
,
Margaret R. Warner
e
, John H. Krege
b
a
University of Sheffield Bone Metabolism Group, Metabolic Bone Centre, Sorby Wing, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK
b
Lilly USA, LLC, Indianapolis, IN, USA
c
University of Alabama, Birmingham, AL, USA
d
Endocrinology, Oschner Clinic Foundation, New Orleans, LA, USA
e
Eli Lilly and Company, Indianapolis, IN, USA
abstractarticle info
Article history:
Received 29 June 2009
Revised 2 November 2009
Accepted 22 December 2009
Available online 6 January 2010
Edited by: F. Cosman
Keywords:
Glucocorticoid-induced osteoporosis
Osteocalcin
Alendronate
Teriparatide
Procollagen type I N-terminal propeptide
(PINP)
Reduced osteoblast function is a primary defect in glucocorticoid-induced osteoporosis (GIO), and is
reflected by decreased biochemical markers of bone formation, such as serum osteocalcin (OC) and
procollagen type I N-terminal propeptide (PINP). This analysis compared the effects of teriparatide and
alendronate on OC and PINP in patients with GIO. In a double-blind study, women (N=159) and men
(N= 38) with GIO were randomized to either teriparatide 20 μg/day by subcutaneous injection or to
alendronate 10 mg/day orally. OC and PINP were measured in fasting-state serum samples obtained at
baseline and at 1, 6, 18, and 36 months. Baseline bone formation markers were below the reference interval
(low) in 33% of patients for OC and in 4% of patients for PINP. On teriparatide therapy, the median OC and
PINP levels increased by 92% and 108%, respectively, and this resulted in only 12% and 1% of patients being
low at 6 months. On alendronate therapy, the median OC and PINP levels decreased by 40% and 53%,
respectively, and this resulted in 68% and 34% of patients being low at 6 months. We conclude that bone
formation as determined by surrogate markers was increased in teriparatide-treated patients with GIO and
decreased in alendronate-treated patients with GIO.
© 2009 Published by Elsevier Inc.
Introduction
Glucocorticoids are frequently prescribed for various inflammato-
ry and/or life-threatening conditions, such as rheumatoid arthritis
and chronic obstructive pulmonary disease [1]. An estimated 0.2% to
0.5% of the general population use glucocorticoids for 3 months or
longer [1]. Glucocorticoid-induced osteoporosis (GIO) is the most
common cause of secondary osteoporosis [2], although the underlying
medical conditions for which glucocorticoids are prescribed, and
other risk factors such as increased age, may also predispose patients
to bone loss and increased fracture risk [3]. Patients taking
glucocorticoids have an increased risk for fracture at any bone
mineral density (BMD), which exceeds the fracture risk predicted by
BMD alone [3,4], suggesting that GIO is characterized not only by bone
loss but also by impaired bone quality [1,5]. With sustained
glucocorticoid administration, reduced bone formation is the most
important pathophysiological feature of GIO. Glucocorticoids inhibit
the differentiation of osteoblasts, while also inducing osteoblast and
osteocyte apoptosis [6,7], which results in a reduced pool of
osteoblasts available to form bone [5]. Histomorphometric analyses
of bone biopsies have found a significantly lower bone formation rate
in glucocorticoid-treated patients compared with women with
postmenopausal osteoporosis [8].
The American College of Rheumatology suggests that patients
treated with glucocorticoids in a dosage equivalent to prednisone
5 mg/day for at least 3 months receive bisphosphonate treatment if
the BMD T score is -1 or lower [9], although the management of each
patient exposed to corticosteroids should be individualized [3].In
theory, bisphosphonates may not be the ideal treatment for GIO
because their anti-catabolic mechanism of action to decrease
osteoclast bone resorption does not address the primary issue of
impaired bone formation during chronic glucocorticoid treatment
[10]. Bisphosphonates have shown the most consistent efficacy in
clinical trials in patients with glucocorticoid-induced osteoporosis. In
previous clinical trials of three different bisphosphonates with BMD as
the primary endpoint, post hoc analyses suggested that bispho-
sphonate therapy reduced vertebral fracture risk compared with
placebo in postmenopausal women with GIO [11].
In contrast, the mechanism of action of recombinant human
parathyroid hormone (1–34) [PTH (1–34); teriparatide], an anabolic
Bone 46 (2010) 929–934
☆
This study was sponsored by Eli Lilly and Company.
⁎ Corresponding author. Fax: +44 1142618775.
E-mail address: r.eastell@sheffield.ac.uk (R. Eastell).
8756-3282/$ – see front matter © 2009 Published by Elsevier Inc.
doi:10.1016/j.bone.2009.12.021
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