Menopause: The Journal of The North American Menopause Society Vol. 21, No. 9, pp. 962/966 DOI: 10.1097/gme.0000000000000197 * 2014 by The North American Menopause Society
Change in arterial stiffness associated with monthly bisphosphonate treatment in women with postmenopausal osteoporosis Michiya Igase, MD, PhD,1,2 Katsuhiko Kohara, MD, PhD,1,2 Yasuharu Tabara, PhD,3 Maya Ohara, MD,1,2 Rie Takita, MD,1,2 Masayuki Ochi, MD, PhD,1,2 Yoko Okada, MD,1,2 and Tetsuro Miki, MD, PhD1,2 Abstract Objective: Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women. In most cases, they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease (CVD). Bisphosphonates (BPs) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density (L-BMD). BPs may also protect against CVD. A single monthly 50-mg dose of minodronate (monthly minodronate) is now common practice and is highly anticipated to reduce the incidence of both bone fracture and CVD. A useful approach to independently predicting CVD is brachial-ankle pulse wave velocity (baPWV). Here, we directly compared the effects of monthly minodronate with those of a standard single weekly 35-mg dose of alendronate (weekly alendronate) on L-BMD and baPWV in postmenopausal women with osteoporosis across a 12-month period. Methods: Thirty-eight postmenopausal women with osteoporosis were randomized into two treatment groups (group 1, weekly alendronate, n = 19; group 2, monthly minodronate, n = 19). L-BMD and baPWV were assessed at baseline and 12-month follow-up. Results: At the end of the 12-month period, increases in L-BMD were similar between group 1 (7.6%) and group 2 (8.5%), but baPWV was significantly reduced in group 2 compared with group 1. The change in baPWV during the study period showed a significant negative correlation with the change in L-BMD. Conclusions: Changes in L-BMD in the monthly minodronate and weekly alendronate groups are generally comparable. Good control of changes in L-BMD in the postmenopausal phase might be associated with regression of CVD. Monthly minodronate is a promising new BP and potential first-line drug for the treatment of osteoporosis in postmenopausal women. Key Words: Minodronate Y Alendronate Y Postmenopausal Y Osteoporosis Y Brachial-ankle pulse wave velocity.
O
steoporosis and atherosclerosis are the two most common diseases in postmenopausal women. Usually, the two diseases are simultaneously present in the same individual and progress insidiously, leading to bone fracture or cardiovascular disease (CVD).1,2 Epidemiological and clinical studies have indicated that estrogen deficiency in postmenopausal women increases the severity of arterial wall stiffness and may increase the rate of CVD,3 and that women with low bone mineral density (BMD) are at significantly greater risk for CVD.4,5
Received September 27, 2013; revised and accepted November 26, 2013. From the 1Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan; 2Anti-aging Center, Ehime University Hospital, Ehime, Japan; and 3Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Funding/support: None. Financial disclosure/conflicts of interest: None reported. Address correspondence to: Michiya Igase, MD, PhD, Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime 791-0295, Japan. E-mail: [email protected]
962
In clinical settings, brachial-ankle pulse wave velocity (baPWV) is widely used as a surrogate marker of atherosclerosis and CVD6,7; an increase in baPWV is one possible cause of the postmenopausal increase in CVD risk.8 Furthermore, a retrospective review of 152 postmenopausal women showed that those with osteoporosis had a significantly higher baPWV than those without, and that a higher baPWV was associated with the presence of atherosclerosis.9 In the treatment of osteoporosis, bisphosphonates (BPs) are considered the first line of therapy and also appear to have the potential to reduce atherosclerosis. BPs inhibit bone resorption and reduce the rates of vertebral and nonvertebral fractures by 40% to 70% and 20% to 35%, respectively.10 Regarding atherosclerosis, BPs interfere with cholesterol synthesis, inflammatory progression, and oxidative stress.11 Among the agents used to inhibit bone resorption, the recently released minodronate is at least 10 times more potent than alendronate.12,13 Comparative trials of minodronate versus alendronate in daily or weekly therapy among women with postmenopausal osteoporosis showed that the two drugs had
Menopause, Vol. 21, No. 9, 2014
Copyright © 2014 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
CHANGE IN ARTERIAL STIFFNESS WITH MONTHLY BP
comparable effects on lumbar spine BMD (L-BMD; L2-L4) and a comparable safety profile for at least 1 year.14,15 These findings suggest that daily administration of minodronate might have a similar efficacy as alendronate in preventing fractures in women with postmenopausal osteoporosis. Minodronate by monthly administration at a dose of 50 mg (monthly minodronate) is presently available in Japan. This dose has a similar efficacy as alendronate by daily administration at 1 mg in terms of L-BMD, bone turnover markers, and tolerability.16 Monthly minodronate may improve medication adherence, thereby reducing the incidence of pathological fractures and atherosclerosis and improving the quality of life of individuals. Here, we directly compared the effects of monthly minodronate treatment with the effects of weekly alendronate treatment at a dose of 35 mg (weekly alendronate) on L-BMD, a bone turnover marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and baPWV in postmenopausal women with osteoporosis. The primary hypothesis of this study was that monthly minodronate treatment would be comparable with weekly alendronate treatment with regard to the mean percent change from baseline in L-BMD, TRACP-5b, and baPWV after 12 months. METHODS Participant enrollment This study was conducted under a prospective, randomized, open-label design. Participants were enrolled in a medical check-up program at the Ehime University Hospital Antiaging Center, which was specifically designed to evaluate aging-related disorders (including atherosclerosis) and physical function.17
Change in arterial stiffness associated with monthly bisphosphonate treatment in women with postmenopausal osteoporosis Michiya Igase, MD, PhD,1,2 Katsuhiko Kohara, MD, PhD,1,2 Yasuharu Tabara, PhD,3 Maya Ohara, MD,1,2 Rie Takita, MD,1,2 Masayuki Ochi, MD, PhD,1,2 Yoko Okada, MD,1,2 and Tetsuro Miki, MD, PhD1,2 Abstract Objective: Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women. In most cases, they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease (CVD). Bisphosphonates (BPs) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density (L-BMD). BPs may also protect against CVD. A single monthly 50-mg dose of minodronate (monthly minodronate) is now common practice and is highly anticipated to reduce the incidence of both bone fracture and CVD. A useful approach to independently predicting CVD is brachial-ankle pulse wave velocity (baPWV). Here, we directly compared the effects of monthly minodronate with those of a standard single weekly 35-mg dose of alendronate (weekly alendronate) on L-BMD and baPWV in postmenopausal women with osteoporosis across a 12-month period. Methods: Thirty-eight postmenopausal women with osteoporosis were randomized into two treatment groups (group 1, weekly alendronate, n = 19; group 2, monthly minodronate, n = 19). L-BMD and baPWV were assessed at baseline and 12-month follow-up. Results: At the end of the 12-month period, increases in L-BMD were similar between group 1 (7.6%) and group 2 (8.5%), but baPWV was significantly reduced in group 2 compared with group 1. The change in baPWV during the study period showed a significant negative correlation with the change in L-BMD. Conclusions: Changes in L-BMD in the monthly minodronate and weekly alendronate groups are generally comparable. Good control of changes in L-BMD in the postmenopausal phase might be associated with regression of CVD. Monthly minodronate is a promising new BP and potential first-line drug for the treatment of osteoporosis in postmenopausal women. Key Words: Minodronate Y Alendronate Y Postmenopausal Y Osteoporosis Y Brachial-ankle pulse wave velocity.
O
steoporosis and atherosclerosis are the two most common diseases in postmenopausal women. Usually, the two diseases are simultaneously present in the same individual and progress insidiously, leading to bone fracture or cardiovascular disease (CVD).1,2 Epidemiological and clinical studies have indicated that estrogen deficiency in postmenopausal women increases the severity of arterial wall stiffness and may increase the rate of CVD,3 and that women with low bone mineral density (BMD) are at significantly greater risk for CVD.4,5
Received September 27, 2013; revised and accepted November 26, 2013. From the 1Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan; 2Anti-aging Center, Ehime University Hospital, Ehime, Japan; and 3Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Funding/support: None. Financial disclosure/conflicts of interest: None reported. Address correspondence to: Michiya Igase, MD, PhD, Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime 791-0295, Japan. E-mail: [email protected]
962
In clinical settings, brachial-ankle pulse wave velocity (baPWV) is widely used as a surrogate marker of atherosclerosis and CVD6,7; an increase in baPWV is one possible cause of the postmenopausal increase in CVD risk.8 Furthermore, a retrospective review of 152 postmenopausal women showed that those with osteoporosis had a significantly higher baPWV than those without, and that a higher baPWV was associated with the presence of atherosclerosis.9 In the treatment of osteoporosis, bisphosphonates (BPs) are considered the first line of therapy and also appear to have the potential to reduce atherosclerosis. BPs inhibit bone resorption and reduce the rates of vertebral and nonvertebral fractures by 40% to 70% and 20% to 35%, respectively.10 Regarding atherosclerosis, BPs interfere with cholesterol synthesis, inflammatory progression, and oxidative stress.11 Among the agents used to inhibit bone resorption, the recently released minodronate is at least 10 times more potent than alendronate.12,13 Comparative trials of minodronate versus alendronate in daily or weekly therapy among women with postmenopausal osteoporosis showed that the two drugs had
Menopause, Vol. 21, No. 9, 2014
Copyright © 2014 The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
CHANGE IN ARTERIAL STIFFNESS WITH MONTHLY BP
comparable effects on lumbar spine BMD (L-BMD; L2-L4) and a comparable safety profile for at least 1 year.14,15 These findings suggest that daily administration of minodronate might have a similar efficacy as alendronate in preventing fractures in women with postmenopausal osteoporosis. Minodronate by monthly administration at a dose of 50 mg (monthly minodronate) is presently available in Japan. This dose has a similar efficacy as alendronate by daily administration at 1 mg in terms of L-BMD, bone turnover markers, and tolerability.16 Monthly minodronate may improve medication adherence, thereby reducing the incidence of pathological fractures and atherosclerosis and improving the quality of life of individuals. Here, we directly compared the effects of monthly minodronate treatment with the effects of weekly alendronate treatment at a dose of 35 mg (weekly alendronate) on L-BMD, a bone turnover marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and baPWV in postmenopausal women with osteoporosis. The primary hypothesis of this study was that monthly minodronate treatment would be comparable with weekly alendronate treatment with regard to the mean percent change from baseline in L-BMD, TRACP-5b, and baPWV after 12 months. METHODS Participant enrollment This study was conducted under a prospective, randomized, open-label design. Participants were enrolled in a medical check-up program at the Ehime University Hospital Antiaging Center, which was specifically designed to evaluate aging-related disorders (including atherosclerosis) and physical function.17
