Imminent Fracture in a Patient with Atypical Femoral Fracture after Prolonged Use of Bisphosphonates

42 Copyright © 2011 The Korean Society of Vascular Neurology

Introduction

Osteoporosis is the main reason that causes fracture, and vari- ous medications are developing in order to treat osteoporosis.

Among them, bisphosphonates are applied to osteoclast and re- duces absorption of bone, and therefore it has been well known as a medicine for improving osteoporosis. This medication has been the most widely prescribed to postmenopausal women and patients who have senile osteoporosis, and has reported that it significantly reduces vertebral and femoral fractures.

However, according to the recent report, when bisphosphonates were used for a prolonged period of time, it can rather increase atypical femoral fracture,

and therefore caution is required, regarding bisphosphonates that are widely used in the field of rehabilita- tion medicine, and if necessary, a change of medicine should be considered as well.

The authors have experienced the imminent fracture, sub- trochanteric microcrack in the opposite region of atypical femo- ral fracture, revealed from the patient with a prolonged use of bis- phosphonates for approximately 5 years, and therefore, it is re- ported with literature review.

Case Report

The 68-year-old woman came to an emergency room due to sudden right hip pain. This patient had sudden pain with a nat- ural “pop” sound without any specific injury or falling history,

when she was coming out from the subway station. Atypical sub- trochanteric femoral fracture was revealed on the radiological test, performed in emergency room (Fig. 1A). All the parts except the right side of femur complaining of pain were found out to be normal on the manual muscle testing and the range of motion test. This patient took risedronate (Actonel

) for approximately 5 years to treat osteoporosis, and the average T-score for lumbar vertebrae and femoral neck were -1.9 and -2.7 respectively on the bone mineral density test which was performed 6 months ago, and the values of bone mineral density were maintained for 2 years (Table 1).

Orthopedic surgeon in this hospital performed open reduc- tion and internal fixation after 5 days of spica (Fig. 1B), and af- ter 2 days of surgery, partial weight bearing and mattress exer- cise including tilt table standing in department of rehabilitation medicine were started. In addition, on the whole body bone scan performed after 1 month of surgery, focal uptake existed in con- tralateral left proximal femur, suggesting the imminent frac- ture, subtrochanteric microcrack in the opposite subtrochanteric area (Fig. 2A). The focal uptake was also sustained 5 months after right subtrochanteric fracture of femur (Fig. 2B). Because atypical femoral fracture might be derived from excessive inhi- bition of bone turnover and inadequate healing of microcrack after the prolonged use of bisphosphonates, the use of the bis- phosphonates was discontinued, and then oral calcium-vitamin D combined formulations and synthetic parathyroid hormone teriparatide (Forsteo

) subcutaneous injection were started.

CASE REPORT

Vascular Neurology 2011;3:42-44 ISSN 2092-6855

Imminent Fracture in a Patient with Atypical Femoral Fracture after Prolonged Use of Bisphosphonates

Young Kwon Yoon,

Sung-Rae Cho

1

Department and Research Institute of Rehabilitation Medicine,

Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea

Received August 17, 2011 Revised September 9, 2011 Accepted September 14, 2011 Correspondence Sung-Rae Cho, MD, PhD Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel +82-2-2228-3715 Fax +82-2-363-2795 E-mail [email protected]

Bisphosphonates have been the most widely prescribed drugs for the treatment of postmenopausal

or senile osteoporosis, and they are highly effective in reducing the risk of vertebral and hip frac-

tures in clinical trials. However, recent case series have implicated a link between prolonged therapy

of bisphosphonates and atypical femoral fractures. A 68-year-old woman underwent sudden right

hip pain without any trauma or falling history. Hip X-ray and pelvic computed tomography revealed

subtrochanteric fracture of femur. She had been prescribed the bisphosphonates for approximately

5 years in order to treat osteoporosis. On the whole body bone scan, imminent fracture, subtrochan-

teric microcrack of left femur also showed an increase of focal uptake, which is symmetrical and

opposite to the atypical fracture. The aim of this report is to present the experience of the imminent

fracture in a patient who had a non-traumatic atypical femoral fracture such as subtrochanteric frac-

ture after prolonged use of the bisphosphonates. Vascular Neurology 2011;3:42-44

Key Wordsaa Osteoporosis, Bisphosphonates, Femoral fracture.

YK Yoon, et al.

43 On the blood tests performed after 4 months of surgery, the

values of osteocalcin and bone alkaline phosphatase, an index of bone formation, and the values of b-CrossLaps and N-telo-

peptide, an index of bone resorption were increased. It was also shown that the level of 25-OH-Vit D was increased from 15.12 ng/mL to 28.36 ng/mL. Because the rate of bone turnover was reduced, the value of parathyroid hormone, which was second- arily increased, was shown to be reduced from 14.49 pg/mL to 5.25 pg/mL (Table 2). After 5 months of surgery, the patient was available for partial weight bearing indoor, and outdoor walk- ing was even possible as well.

Discussion

Formation and resorption of bone progress through courses of bone development and growth, and remodeling process dis- placing old bones into new bones. Such remodeling is depen- dent on the detailed balance of osteoblast and osteoclast. In other words, osteoporosis from menopausal women is caused by an excess of bone resorption by osteoclast, rather than bone for- mation by osteoblast.

Bisphosphonates are not only the most useful medicine for the treatment of osteoporosis, but also widely used in various bone-related diseases including osteogenesis imperfecta, Paget’s disease, fibrous dysplasia, and multiple myeloma.

Reports re- garding therapeutic effects showed that the bone mineral den- sity of vertebrae was increased by 7% as compared to the placebo Table 1. T-score of bone mineral density in the patient with atypical

femoral fracture

Region 2 years before fracture (T-score)

6 months before fracture (T-score)

L1-L4 -2.0 -1.9

Femur neck -2.8 -2.7

Trochanter -1.5 -1.5

Total hip -1.6 -1.7

Wards -3.7 -3.7

L: lumbar spine.

Table 2. Laboratory findings in the patient with atypical femoral fracture

1 week after fracture

4 months after fracture

Calcium (mg/dL) 07.6 09.7

25-OH-Vit D (ng/mL) 15.12 28.36

PTH (pg/mL) 14.49 05.25

Bone ALP (ng/mL) 13.8 17

Osteocalcin (ng/mL) 29.22 30.22

b-CrossLaps (ng/mL) 00.142 00.184

N-telopeptide (nM/mM) 07.4 18.3

25-OH-Vit D: 25-hydroxy vitamin D, PTH: parathyroid hormone, Bone ALP: bone alkaline phosphatase.

A B

Figure 2. Whole body bone scan findings of the patient with atypi- cal femoral fracture. Focal uptake (arrow) existed in contralateral left proximal femur (A). The focal uptake (arrow) was sustained 5 months after right subtrochanteric fracture of femur (B), suggesting that prolonged use of the bisphosphonates caused microcracks.

A B

Figure 1. The hip X-ray findings of the patient with atypical femoral fracture. A: subtrochanteric fracture (arrow) of femur, right side. B: post-op-

erative hip X-ray finding (arrow) after open reduction and internal fixation.

Atypical Fracture after Bisphosphonate

44 Vascular Neurology 2011;3:42-44

group for 3 years of treatment, and for most cases of femoral bone density, it was increased by 4% as compared to the placebo group, and it also reduced biochemical indicator of bone re- sorption.

Despite such usefulness, bisphosphonates are not metabolic inside the body but rather accumulated in skeletal tissue, and so for the prolonged use, the problem which will negatively influ- ence on the bone has been raised. In other words, in the studies regarding the prolonged use of bisphosphonates, it was report- ed that the bone turnover was inhibited, leading to accumula- tion of microcrack, and growth of collagen is interrupted lead- ing to problems in fracture healing.

Odvina et al.

reported that, when alendronate was taken for a prolonged period of time for average 7.3 years, a significant increase in low-energy subtroch- anter and femoral shaft fracture, as compared to intertrochanter and femoral neck fracture on the radiographic studies. In addi- tion, Lenart et al.

verified that, in subtrochanter and femoral shaft fracture group, the rate of bisphosphonates use for a pro- longed period was higher. However, there is still a debate going on that other studies reported that, although bisphosphonates were used for a prolonged period of time, the bone mineral den- sity of atypical femoral fracture did not increase so much.

In the case of this patient, bisphosphonates were taken for ap- proximately 5 years, and the fact that subtrochanter fracture oc- curred without any trauma cannot exclude the possibility of aty- pical femoral fracture due to prolonged use of bisphosphonates.

According to the recent study by Schilcher et al.

the absolute rate of atypical femoral fracture due to prolonged use of bisphosph- onates was reported to be low. However, in this case with aty- pical femoral fracture, the opposite side of subtrochanteric re- gion, which has shown no definite fracture, also showed an im- minent fracture on the whole body bone scan. Therefore, it will

be required to discontinue the bisphosphonates or prevent ob- vious fracture by changing treatment strategy.

Acknowledgments

This study was supported by grants from National Research Foundation (NRF-2010-0020408; 2010-0024334) funded by the Ministry of Science and Technology, Republic of Korea.

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