Inhalation Therapy of Calcitonin Relieves Osteoarthritis of the Knee

다국어 초록 (Multilingual Abstract)

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1β, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20)received a home exercise program for 6 months. Compared with baseline, while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.

참고문헌 (Reference)

1 Meulenbelt I, "Urinary CTX-II levels are associated with radiographic subtypes of osteoarthritis in hip, knee, hand, and facet joints in subject with familial osteoarthritis at multiple sites: the GARP study" 65 : 360-365, 2006

2 Manicourt DH, "Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions" 42 : 1159-1167, 1999

3 Sellam J, "The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis" 6 : 625-635, 2010

4 Hayami T, "The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model" 50 : 1193-1206, 2004

5 Lotz M, "The role of nitric oxide in articular cartilage damage" 25 : 269-282, 1999

6 Fernandes JC, "The role of cytokines in osteoarthritis pathophysiology" 39 : 237-246, 2002

7 Karsdal MA, "The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study" 18 : 150-159, 2010

8 Sondergaard BC, "The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model" 56 : 2674-2678, 2007

9 Ofluoglu D, "The effect of calcitonin on beta- endorphin levels in postmenopausal osteoporotic patients with back pain" 26 : 44-49, 2007

10 Karsdal MA, "Should subchondral bone turnover be targeted when treating osteoarthritis?" 16 : 638-646, 2008

11 Di Nino DL, "Positive regulation of endochondral cartilage growth by perichondrial and periosteal calcitonin" 144 : 1979-1983, 2003

12 van Baar ME, "Pain and disability in patients with osteoarthritis of hip or knee: the relationship with articular, kinesiological and psychological characteristics" 25 : 125-133, 1998

13 Lyritis GP, "Pain Relief From Nasal Salmon Calcitonin I . n Osteoporotic Vertebral Crush Fractures" 275 : 112-114, 1997

14 Manicourt DH, "Oral salmon calcitonin reduces Lequesne’s algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis" 54 : 3205-3211, 2006

15 Bagger YZ, "Oral salmon calcitonin induced suppression of urinary collogen type II degradation in postmenapausal women: A new potential treatment of osteoarthritis" 37 : 425-430, 2005

16 Ito A, "Mechanisms for ovariectomy-induced hyperalgesia and its relief by calcitonin: participation of 5-HT1A-like receptor on C-afferent terminals in substantia gelatinosa of the rat spinal cord" 20 : 6302-6308, 2000

17 Sondergaard BC, "Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes" 11 : 62-, 2010

18 Dam EB, "Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI" 17 : 384-389, 2009

19 Petrella RJ, "Home based exercise therapy for older patients with knee osteoarthritis: a randomized clinical trial" 27 : 2215-2221, 2000

20 Franchimont P, "Effects of human and salmon calcitonin on human articular chondrocytes cultivated in clusters" 69 : 259-266, 1989

21 Evcik D, "Effectiveness of a home-based exercise therapy and walking program on osteoarthritis of the knee" 22 : 103-106, 2002

22 Badurski J, "Comparative analysis of three treatment regimens for treating gonarthritis with calcitonin, naproxen and flavonoids based on EULAR criteria and visual analogue scale (VAS)" 50 : 37-40, 1995

23 Meulenbelt I, "Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study" 15 : 379-385, 2007

24 Suzuki H, "Calcitonin-induced changes in the cytoskeleton are mediated by a signal pathway associated with protein kinase A in osteoclasts" 137 : 4685-4690, 1996

25 Karsdal MA, "Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?" 14 : 617-624, 2006

26 Shyu JF, "Calcitonin induces podosome disassembly and detachment of osteoclasts by modulating Pyk2 and Src activities" 40 : 1329-1342, 2007

27 Sondergaard BC, "Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes" 14 : 759-768, 2006

28 Takayama B, "An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats" 9 : 164-, 2008

29 Bredella MA, "Accuracy of T2-weighted fast spinecho MR imaging with fat saturation in detecting cartilage defects in the knee: comparison with arthroscopy in 130 patients" 172 : 1073-1080, 1999

30 Reijman M, "A new marker for osteoarthritis: cross-sectional and longitudinal approach" 50 : 2471-2478, 2004