Bone turnover markers and the factors associated with atypical femur fractures among Japanese patients.
Many previous reports have indicated that atypical femur fractures (AFFs) are associated with the administration of bisphosphonates (BPs). A number of risk factors and hypotheses regarding the pathogenesis of AFFs have been reported to date. The purpose of the present study was to identify the factors associated with AFFs in Japanese individuals and to elucidate the association between bone metabolism and AFFs by evaluating bone turnover markers (BTMs). We prospectively reviewed all patients with femur fractures and identified the patients with AFFs and typical femur fractures (TFFs). We collected the demographic and clinical data that were relevant to the present study, namely age, gender, affected side, affected site, concomitant medical history, and comorbid conditions, and measured the levels of BTMs within 24h after trauma. Welch's test and Fisher's exact probability test were used for the statistical analyses. A total of 338 patients, including 10 patients with AFFs and 328 patients with TFFs, were analyzed under the inclusion criteria. The use of BPs (p<0.001) and collagen disease and chronic granulomatous disease (CD/CGD) (p=0.025) were more frequently observed in patients with AFFs than in patients with TFFs, while the levels of BTMs, including N-terminal propeptides of type 1 procollagen (P1NP), isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) and undercarboxylated osteocalcin (ucOC) were significantly lower in patients with AFFs than in patients with TFFs. Furthermore, the level of TRACP-5b was found to be significantly lower in patients with atypical subtrochanteric fractures than in atypical diaphyseal fractures (p=0.025). Moreover, the levels of P1NP (p=0.016) and TRACP-5b (p=0.015) were found to be significantly lower in patients with AFFs than in patients with TFFs in a subgroup analysis of BPs users. The use of BPs was considered to be a factor associated with AFFs. Our comparison of the BTMs in patients with AFFs and TFFs indicated that the severe suppression of bone turnover was associated with the pathogenesis of AFFs. The extent of the influence of suppressed turnover on the pathogenesis of AFFs may differ depending on the fracture site.
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan. Electronic address: yoiizuka@gunma-u.ac.jp.
Yoichi
Y
Iizuka
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Haku
H
Iizuka
Department of Orthopaedic Surgery, Inoue Hospital, 55, Torimachi, Takasaki, Gunma 370-0053, Japan.
Tetsuya
T
Kaneko
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Tokue
T
Mieda
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Gunma Cardiovascular Center, 3-12, Ko, Kameizumimachi, Maebashi, Gunma 371-0004, Japan.
Rumi
R
Takechi
Department of Orthopaedic Surgery, Gunma Cardiovascular Center, 3-12, Ko, Kameizumimachi, Maebashi, Gunma 371-0004, Japan.
Hideki
H
Suzuki
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Maebashi Red Cross Hospital, 3-21-36 Asahimacho, Maebashi, Gunma 371-0014, Japan.
Yasunori
Y
Sorimachi
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopedic Surgery, Isesaki Municipal Hospital, 12-1, Tsunatorihonmachi, Isesaki, Gunma 372-0817, Japan.
Takahito
T
Suto
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopedic Surgery, Isesaki Municipal Hospital, 12-1, Tsunatorihonmachi, Isesaki, Gunma 372-0817, Japan.
Masahiro
M
Tachibana
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Takasaki General Medical Center, 36, Takamatsucho, Takasaki, Gunma 370-0829, Japan.
Tomotaka
T
Yoneyama
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Fujioka General Hospital, 942-1, Fujioka, Fujioka, Gunma 375-8503, Japan.
Takuya
T
Omodaka
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Gunma Chuo Hospital, 1-7-13, Kouncho, Maebashi, Gunma 371-0025, Japan.
Shogo
S
Hashimoto
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Gunmaken Saiseikai Maebashi Hospital, 564-1, Kamishindenmachi, Maebashi, Gunma 371-0821, Japan.
Noritaka
N
Hamano
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Tone Central Hospital, 1855-1, Higashiharashinmachi, Numata, Gunma 378-0053, Japan.
Hideo
H
Sakane
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Takasaki General Medical Center, 36, Takamatsucho, Takasaki, Gunma 370-0829, Japan.
Daisuke
D
Shimoyama
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Maebashi Red Cross Hospital, 3-21-36 Asahimacho, Maebashi, Gunma 371-0014, Japan.
Isaku
I
Kohama
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Gunma Chuo Hospital, 1-7-13, Kouncho, Maebashi, Gunma 371-0025, Japan.
Atsufumi
A
Ohshima
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Gunmaken Saiseikai Maebashi Hospital, 564-1, Kamishindenmachi, Maebashi, Gunma 371-0821, Japan.
Tatsuya
T
Nozaki
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, 6-3, Kiryu Kosei General Hospital, Orihimecho, Kiryu, Gunma 376-0024, Japan.
Masataka
M
Kamiyama
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopedic Surgery, Isesaki Municipal Hospital, 12-1, Tsunatorihonmachi, Isesaki, Gunma 372-0817, Japan.
Tomohiko
T
Moteki
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Fujioka General Hospital, 942-1, Fujioka, Fujioka, Gunma 375-8503, Japan.
Asuka
A
Ohshima
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Saint Pierre Hospital, 786-7, Kamisanomachi, Takasaki, Gunma 370-0857, Japan.
Shuhei
S
Takamine
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Public Tomioka General Hospital, 2073-1, Tomioka, Tomioka, Gunma 370-2393, Japan.
Akira
A
Honda
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan; Department of Orthopaedic Surgery, Zenshukai Hospital, 1381, Ninomiyamachi, Maebashi, Gunma 379-2117, Japan.
Akira
A
Ueno
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Tsuyoshi
T
Tajika
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Koichi
K
Okamura
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Toshiro
T
Warita
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Yukio
Y
Yonemoto
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Hitoshi
H
Shitara
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Takashi
T
Ohsawa
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma 371-8511, Japan.
Kenji
K
Takagishi
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016723:Bone Remodeling / Q000187:drug effects; D003095:Collagen Diseases / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D015897:Comorbidity; D003430:Cross-Sectional Studies; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D005264:Femoral Fractures / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D017102:Fracture Healing / Q000502:physiology*; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology*; D010446:Peptide Fragments; D011347:Procollagen; D011446:Prospective Studies; D012307:Risk Factors; D000071681:Tartrate-Resistant Acid Phosphatase
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; C000605510:ACP5 protein, human; D000071681:Tartrate-Resistant Acid Phosphatase
Atypical femur fractures; Bone turnover makers; Pathogenesis