GAG 研究:TOWNSEND LETTER 美國醫學期刊 (9) 膝關節炎的臨床研究

膝關節炎的臨床研究 Gonarthrosis A Pilot Study



患者和研究方法
該研究包括120名患者,有X光放射線照相證實是膝關節炎且表現出疼痛臨床症狀的患者。性別分布是64名男性和56名女性組成了這一群體。年齡分佈從37歲到91歲不等,大多數患者都是六七十歲的銀髮族,年齡分佈如圖10所示。


79名患者為膝內翻(bowlegged),另外39名為膝外翻(knock kneed)。兩類患者混合,而兩者病狀皆有的也是有。有幾個嚴重到是需要被轉到外科進行人工膝關節置換術。其中一名患者是被他的心臟病專家轉過來,建議在考慮完全人工關節置換之前,應諮詢有經驗的關節炎管理醫生,因為從他的角度來看,這位患者不是一個安全的手術候選人。

Patients and methods
 One hundred and twenty (120) referred patients suffering from radiographically confirmed arthritis of the knee and showing clinical symptomatology of pain were included in this study. Sixty-four males and fifty-six females made up this group. Ages ranged from thirty-seven to ninety-one. Most of the patients were in their sixties and seventies. Age distribution by decades is shown in Figure 10.
Seventy-nine patients were genu varus (bowlegged), thirty-nine were genu valgus (knock kneed).Two patients were mixed, having both. Several were referred for total knee replacement. One of the patients was referred by his cardiologist suggesting that an experienced doctor in arthritic management should be consulted prior to considering total joint replacement since, from his perspective, the patient was not a safe candidate for surgery.

研究中的所有患者都獲得了有關使用青邊貽貝治療退化性關節炎的衛教資訊。他們被告知青邊貽貝已被證明具有與 Indocin (一種消炎止痛藥) 相同的抗發炎作用,但更顯著的是青邊貽貝具有營養代謝作用,強調了粘多醣(醣胺聚醣)在蛋白多醣軟骨形成中的重要性。

患者也會閱讀軟骨的蛋白多醣結構,了解硫酸軟骨素、硫酸鹽角質素和透明質酸如何與連接蛋白結合以形成軟骨蛋白多醣模型。 (參見圖1)他們還被鼓勵閱讀醫學博士 Jason Theodosakis 的書籍 The Arthritis Cure,認知青邊貽貝的功能、強化認知是關節炎治療的一部分。


對海鮮、貝類或紫花苜蓿已知過敏的患者被排除在本研究之外。允許服用特定抗炎藥或止痛藥的患者繼續服用,但要求記錄服用的所有藥物。

All patients in the study were provided information on the use of Perna mussel for degenerative joint disease.They were advised that Perna had been shown to have an anti-inflammatory effect equal to that of Indocin, but more significantly it had a nutritive metabolic effect. The importance of mucopolysaccharides (glycosamino- glycans) in the formation of basic proteoglycan cartilage was stressed. The patients were shown illustrations indicating the architecture of a cartilage proteoglycan showing how chondroitin sulfate, keratin sulfate and hyaluronic acid combine with a link protein to make a cartilage proteoglycan model. (See Figure 1) They were encouraged to read the popular book The Arthritis Cure by Jason Theodosakis, MD, to reinforce the message that certain oral chondroprotective products were finding acceptance as part of the treatment of arthritis.
Patients with a known allergy to seafood, shellfish or alfalfa were excluded from this study. Patients who were taking some form of nonsteroidal anti-inflammatory or pain medication were allowed to continue but were requested to keep a record of all medications required.

疼痛評估
患者使用 Huskinson 視覺模擬疼痛量表來評估疼痛,疼痛強度範圍為1到10(參見圖11),從無疼痛到最壞可能的疼痛,運用此方式在整個研究中監測疼痛評分。 如果疼痛在視覺模擬量表上表示為高於5,則首先在關節內注射 Triamcinolone 40mg、Dexamethasone 6mg 和 Marcaine 0.5% 3cc,用於先短暫緩和患者的疼痛。



Pain Assessment
The Huskinson visual analogue pain scale was used by the patient to assess pain." The pain intensity ranges from "no pain to worst possible pain" on a scale of 1 to 10 (See Figure 11). Pain scores were monitored throughout the study. If pain was expressed as above 5 on the visual analogue scale an initial injection of Triamcinolone 40 mg, Dexamethasone 6 mg, and Marcaine 0.5 % 3 cc , was given intra - articularly .

生物力學調整
患有膝內翻(bow leg)的患者,轉給當地鞋匠製作的1/8外鞋跟和1/8外鞋底。 膝外翻 (knock knee) 的患者則訂製1/8內鞋跟和1/8內鞋底。

Biomechanical Adjustment
Patients with genu varus (bow leg) were referred to a local shoemaker for 1/8" outer heel wedges and 1/8" outer sole wedges. Patients with genu valgus (knock knee) were referred for 1/8 inner heel wedges and 1/8" inner sole wedges.

發炎指數
根據腫脹、創傷、發紅、疼痛和發熱的臨床證據,是用來估計關節的總體發炎活動狀況,這與 Hippocrates 希波克拉底(古希臘伯里克利時代之醫師) 描述的 Dolor (疼痛)、Rubor (發紅)、Color (熱)、Tumor (腫脹) 差不多。有「晨僵」(早上起來會覺得身體僵硬)的人必須自行紀錄日常運動,包含參加哪些運動(如高爾夫球)、使用手杖或護膝的狀況。醫生則在每次就診時進行評估(優良、良好、無變化),並告知消炎藥、止痛藥、外用凝膠使用的注意事項。

Inflammatory Index
An estimate of overall inflammatory activity of the joints based upon clinical evidence of swelling, trauma, redness, pain and heat was made. This differs very little from Hippocrates' "Dolor (pain), Rubor (redness), Color (heat) and Tumor (swelling)." A history of "minutes of morning stiffness" as well as daily activity, participation in sports, golf,etc. was recorded by the patients
Notes were made as to the use of a cane or a knee brace. The patient's opinion of their condition in comparison with their initial state (the same, a little better, a lot better, worse, much worse) was recorded. The physician's evaluation was also made at the time of each visit (excellent, good, no change). Notes were made as to tolerance of Perna and compliance. Notes were also made in reference to the use of NSAIDS (nonsteroid anti-inflammatory drugs), pain medication, topical creams or ointments. 

X光射線評估
該研究會在一開始拍攝站立時的膝關節X光片(AP),隨後在2個月、6個月和1年追蹤拍攝以用來比較。建立這樣一個X光片追蹤平台,可以有一標準來觀察患者的膝關節變化。該平台的放射線照相鏡頭被定位與地板水平,並將放射線照相鏡頭置於80 am的位置、聚焦在患者髕骨的中心。

為了保持同一患者的後續都站在的相同位置,患者第一次站立時腳部會被繪製好輪廓,製作成專屬模板,以便後續由X光拍攝人員可以將模板放置相同位置後,患者依照輪廓站立,確保每次都是在平台上完全相同的位置。

X-ray Evaluation 
Standing, weight bearing AP views of both knees were taken initially, at two months, six months and one year. A special platform was built so that the patient could be positioned in a standard and reproducible manner. The radiographic tube was positioned so the central ray of the X-ray beam was horizontal and parallel to the floor. The tube was kept set 80 am distance from the X-ray cassette. The center of the X-ray beam with the aid of the tube positioning light was focused on the center of the patient's patella. 
In order to keep the same position for subsequent films of the same patient, an outline of the patient's feet was made with the patient standing on his/her own X-ray folder. This folder was always placed by the X-ray technician in exactly the same position on the platform.

患者每天服用3顆青邊貽貝提取物膠囊(1500毫克)。該研究中使用的產品,每顆膠囊含有500毫克青邊貽貝和100毫克苜蓿。該研究目標是持續一年,患者在第一次使用後會持續追蹤健康狀況並被隨訪。在120名患者中,只有11名患者最終選擇了人工膝關節置換術,大多數其他患者繼續表現良好並繼續服用青邊貽貝膠囊以持續關節代謝和保護軟骨。

The patients were prescribed three Perna capsules (a total of 1500 mg of Perna canaliculus), per day taken with food, then two capsules per day as permanent maintenance dosage. The product used in the study contained 500 mg green-lipped mussel (Perna) and 100 mg alfalfa. 
The study was designed to last one year. Most patients continued to be followed subsequent to that time. Out of 120 original patients only eleven patients eventually elected total knee replacement. Most of the other patients continued to do well and continued to take the Perna capsules (two daily) for ongoing metabolic and chondro- protective support.

患者評估
首次就診後一個月醫師會開始與患者問診及追蹤狀況。根據這個研究計劃,醫生每2~3個月就會問診一次,並在一年後做出最終評估。使用 Kellgren 和 Lawrence 系統,根據 I 至 IV 的等級對患者的X射線進行分級 - 骨性關節炎的程度從輕微的1級到嚴重的4級,分級的嚴重程度描述如下:


Grade according to Kellgren & Lawrence
Number of Patients
Increasing
I
25
Severity
II
76
Of
III
12
Osteoarthrits
IV
7

Patient Assessment 
The patients were seen for follow-up one month after the initial visit. Subsequent to that date, depending on their program, they were seen every two to three months. A final assessment was made after one yearX-rays of the patients were graded on the basis of a scale of I to IV using the Kellgren and Lawrence system - Degree of osteoarthritis progressing by grade from Grade 1, minimal, least severe, to Grade IV being bone on bone. The grade of severity in this group is described as follows: 

在第一次隨訪時這些患者對醫生的反應變得熱絡。 許多I級和II級患者的初始模擬疼痛等級為 7,但後續紀錄為 0~2,這些患者在研究的後期繼續保持舒適和活躍,並在剩餘的就診期間,醫生注意到疼痛、發熱和腫脹的證據顯著減少或消失。 甚至幾名患者的動機只是為了獲得新的青邊貽貝供應,與醫生討論並表現出對X射線可能改善的好奇心,其中使用手杖的兩名患者已經不再需要它們。

The response to management in these groups of patients studied became evident at the time of the first follow-up visit. Many of the Grade I and II patients who had presented with an initial analogue pain scale of 7 reported a 0 to 2. These patients continued to remain comfortable and active during the rest of the study. Evidence of pain, heat and swelling was noted to be significantly diminished or absent during the remaining visits. Motivation in several patients was simply to get a new supply of Perna, to visit with the physician and to manifest curiosity as to possible improvement in X-rays. The two patients who were using canes no longer required them.

患者的年齡、性別、膝內翻或膝外翻的存在,似乎與治療反應沒有顯著關係,但疾病的嚴重程度很重要。青邊貽貝提取物在 Kellgren I級和 II 級非常有效,但在III級和IV級效果較差, IV級是最嚴重的狀況。

大部分患者能夠將 NSAIDs 這類消炎藥減少50%或更多。隨著醫生繼續問診這些患者時,也注意到疼痛藥物使用量減少,大多數患者報告他們的病情得到了很大改善,且沒有患者抱怨他的問題更嚴重。之前有9名患者抱怨使用青邊貽貝感覺包括腹脹、吐氣時有海鮮腥味。因此建議他們服用含有氨基葡萄糖和硫酸軟骨素的其他產品,但不包括在本研究分析中。

本研究中的患者(共120人)報告他們得到很大改善(95人)或有所改善(16人),而上述9名患者報告沒有變化(圖12)。


本研究中,根據參與研究的醫生觀察這些患者有19名(27%)覺得沒有表現出改善、38名(31%)覺得表現出良好的改善,大部分覺得63名(52%)表現出了極好的改善(圖13)。


The age and sex of the patients, the presence of genu varus or genu valgus did not appear to have a significant relation to therapeutic response.The degree of severity of disease was important. Perna was seen to be very effective in Kellgren Grade I and II, less effective in Grade III and IV. Grade IV is bone on bone (most severe).
A significant number of patients were able to reduce their NSAID intake by 50 % or more . Pain medication was also noted to be less as patients continued to be followed. Most patients reported that their condition was much improved. No patient complained that his problem was worse. Nine previous patients complained of side effects from Perna consisting of bloating, gas indigestion, and the fishy taste. They were advised to take other products containing glucosamine and chondroitin sulfate and were not included in this study analysis. 
Patients remaining in this study (a total of 120) reported that they were either much improved (95) or some improved (16).
Nine of the patients in this study reported no change (Figure 12). According to this practitioner, nineteen ( 27 % ) showed no improvement ( no change ) , thirty - eight ( 31 % ) showed good improvement and sixty - three ( 52 % ) were reported as having made excellent improvement( Figure 13).

這次研究都沒有患者在過程中失去聯繫。這一事實區別在大學醫院門診完成研究的差異。我作為這項研究的醫生,我對所有這些患者非常熟悉,甚至會在街上認出他們,並且會對他們病情的進展有一個最新印象。

本研究中的17名患者,之前就曾接受人工膝關節置換術。這些患者對未動手術的另一個膝關節仍有疼痛症狀,如果可能的話他們當時應避免膝蓋手術。畢竟手術都有風險,最常見的是零件磨損和鬆動,這些患者其實都不需要額外的人工膝關節重建。

但在這次的研究中,有11名患者最終還是接受了關節置換治療,但覺得已經購買了青邊貽貝的方案,因此這些患者在一開始投入研究時,已計劃一年後進行手術。 另外5名患者最終需要進行關節鏡清創術、7名患者進行了關節內注射透明質酸(玻尿酸),其中五個效果很好。然而,兩名患者發生急性異物反應,需要全膝關節置換。

No patients were lost at follow-up. This fact reflects the major difference from studies done in a university hospital outpatient facility. As the sole physician involved in this study, I became quite familiar with all of these patients, would recognize them on the street and would have a knowledgeable up to date impression of their progress.
Seventeen patients in this study had previously undergone total knee replacement performed previously by the author. These patients were symptomatic on the unoperated knee and were anxious to avoid knee surgery if at all possible. Joint replacement is not accomplished without risk, the most common çomplication is component wear and loosening. None of these patients required additional total knee reconstruction.
 Eleven patients in thia study did eventually come to joint replacement therapy but felt that the Perna protocol had bought them some time. These patients were scheduled for surgery after the initial study period limit, one year. Five patients eventually required arthroscopic debridement. Seven patients have had intra-articular injection of hyaluronic acid. Five of them with good results. Two patients however developed an acute foreign body reaction which necessitated total knee replacement. 


X光射線發現 - 漸進關節間隙縮小的逆轉

放射學評估顯示,部分患者可逆轉關節間隙變窄的情況。X光放射線照片在關節空間以毫米為單位,選定 C 點和 P 點測量膝內翻的內側脛股關節間隙。C 點是關節中最窄的空間,P是股骨的最內側邊緣(圖14)在患者的骨關節炎膝關節進行側向測量。


例如,圖15 和16 顯示了在不同時間拍攝的53歲男性和51歲女性的X光射線。



透過X射線分析,本研究中的8名患者被發現關節間隙變窄的狀況可漸進性逆轉。圖15中的男性患者在C點的關節間距中有1.2 mm的逆轉(1997年7月25日為3.0 mm,而1998年10月11日為4.2 mm)。圖16中的女性患者也有逆轉C點的接頭間距為1.2 mm(1998年1月30日為3.0 mm,而1999年7月3日為4.2 mm)。 

根據Lequesne報導,對於膝關節退化性骨關節炎患者,C 點每年平均關節間隙損失為 0.26 mm。本研究中患有I級或II級骨關節炎的患者在一年的研究過程中未發現關節間隙縮小。 III級和IV級患者的X射線確實顯示關節間隙縮小的證據,儘管作為實例給出的兩名III級患者實際上顯示出逆轉。所有需要關節重建的患者都被評為IV級骨骼骨骼。

X-ray Findings-Reversal of Progressive Joint Space Narrowing
Radiographic evaluation showed that some patients had reversal of the narrowing of the joint space of the tibial femoral joint. An architect's caliper with a stabilizing screw and sharp points placed on the radiographic joint space was used to measure joint in millimeters. The medial tibiofemoral joint space in genu varus was measured at Point C and P. Point C being the narrowest space in the joint, P being the most medial edge of the femur (Figure 14) Lateral measurements were made in osteoarthritic knees of patients with both genu vaigus and genu varus. As an example, standing X-rays of a 53 year old male and a 51 year old female taken at different times are shown in Figure 15 and 16.
Eight patients in this study were found to have reversed the progressive joint space narrowing usually found in osteoarthritic patients as seen by X-ray analysis. The male patient in Figure 15 had a reversal of 1.2 mm in the joint spacing in Point C (3.0 mm on 7/25/97 versus 4.2 mm on 10/11/98).The female patient in Figure 16 also had a reversal of 1.2 mm in the joint spacing at Point C (3.0 mm on 1/30/98 versus 4.2 mm on 7/3/99). Lequesne reported a mean joint space loss in Point C of 0.26 mm per year is typical for patients with osteoarthritis of the knee. Patients in this study with Grade I or II osteoarthritis were not found to show increased joint space narrowing during the course of the one year study. X-rays of patients with Grade III and IV did show evidence of increased joint space narrowing although the two Grade III patients given as examples actually showed reversal. All patients who required joint reconstruction were found to be rated as Grade IV, bone on bone. 

關節軟骨的軟骨形成再生
X光射線顯示8名患者的關節間隙縮小產生逆轉,以及I級和II級骨關節炎患者關節間隙保持穩定不惡化,強烈顯示青邊貽貝有刺激軟骨形成的代謝作用,一名患者在關節鏡下清除時,發現這一結果的確是正確的。這名患者原本發現有一個大的軟骨破損,在關節鏡觀察時似乎已經重新生成新的軟骨,外觀好像缺陷是用新鮮的乳膠漆填充的。

Chondrogenesis Regrowth of Articular Cartilage 
X-ray findings showing a reversal of progressive joint space narrowing in eight patients and stabilization of the joint spaces in patients with Grade I and II osteoarthritis strongly suggested an anabolic effect of Perna stimulating chondrogenesis. This was supported by the findings in one patient at the time of arthroscopic debriedment .This patient was found to have a large ostiochondral defect, which appeared to have been overgrown by new viable cartilage. The appearance was as if the defect had been filled with a fresh latex paint.

生物力學效應
很少發現關節炎患者之前曾接受過生物力學的評估和治療,幸運的是穿鞋子是明智的,許多患者可以將適當的鞋墊放入鞋中,多數鞋子都可以透過鞋商客製鞋墊,但高跟鞋必須避免。 患有I級或II級關節炎的患者對這種簡單的方案接受度很高,並且可能期望減少他們對NSAIDs這類消炎藥的使用。繼續使用青邊貽貝膠囊和鞋墊是適當管理膝關節骨關節炎的永久性建議。只是大多數患者對鞋墊支撐和矯形器仍不滿意,儘管現在的技術水平非常好。 開發用於支撐關節的護具技術是非常有效的,但除非確定患者避免手術,否則很難獲得患者的依賴性。

Biomechanical Effects 
Patients are seldom found who have been previously evaluated and treated for biomechanical factors involved in their disease process. Experience has shown that many patients benefit from having the appropriate wedges put into their shoes. Fortunately, present day shoe wear is sensible and most shoes can be worked with by a competent shoe maker High heels must be avoided. The patients with Grade I or II arthritis respond to this simple regime and may expect to decrease their use of NSAIDS. The continued use of Perna capsules and the shoe wedges is a permanent recommendation for proper management of osteoarthritis of the knee.
Most patients are not happy with bracing and orthotics although the present day state of the art is excellent. Techniques for developing unloader braces for relief of the genu varus-genu valgus stress are quite effective. Compliance is difficult to obtain unless a patient is determined to avoid surgery. 


關節內註射透明質酸(玻尿酸)
在該研究中,關節內注射透明質酸(玻尿酸)使一些患者獲得暫時舒緩,並且在一些情況下非常顯著,但大多數II級或IV級患者沒有經歷過這種手術。30名患者中的3名患者對注射產生急性發炎反應,其中導致兩個需要全膝人工關節置換術,並且發現其具有急性異物反應的臨床證據。

Intra-articular Injection of Hyaluronic Acid 
Intra-articular injection of hyaluronic acid benefited a few patients in this study group and in some cases, quite significantly. Most patients with Grade II or IV have not experienced lasting benefit from this procedure. Three patients out of thirty patients developed an acute inflammatory reaction to the injection. Two of these required total knee replacement and were found to have clinical evidence of an acute foreign body reaction.

關節鏡
關節鏡檢查通過各種微創技術關節鏡成為一種廣泛接受的治療膝關節骨性關節炎的方法,該操作的主要特點是沒有植入異物。 因此,對於希望繼續參加運動或從事需要劇烈活動的職業的年輕患者來說,這是令人滿意的外科手術。缺點是如果關節炎已經過於嚴重,該手術可能不會產生長期影響。如果有軟骨磨損、骨折等檢查證據,建議將人工關節置換作為治療選擇。

Arthroscopy 
Arthroscopy has definitely guided decisions made as to whether the patient may benefit from a high proximal tibial osteotomy. Upper tibial osteotomy, by various techniques is a widely accepted method of treatment for osteoarthritis of the knee. The major disadvantage of this operation is that no foreign material is implanted. Thus for younger patients who wish to continue playing sports or to engage in occupations requiring vigorous activity it is a satisfactory surgical procedure. The disadvantage is that if the arthritic process is too far advanced, the procedure may not have long-lasting effects. If there is arthroscopic evidence of cartilage loss, osteochondral fracture etc., total joint replacement has been recommended as the treatment choice.


討論結果
本研究中使用青邊貽貝治療膝關節炎的患者產生陽性反應最令人鼓舞。因此,在實務中對這些患者進行管理的改進方法已經發展出來,如下。

如上所述,在最初的患者病史諮詢和包括X射線檢查在內的完整體檢後,本研究中的所有患者均在青邊貽貝提取物使用後開始追蹤。大多數人一直允許繼續NSAIDs這類消炎藥,如果在視覺模擬量表上疼痛表達為高於5,則會在注射消炎止痛藥,讓患者盡快獲得緩解。使用青邊貽貝和適當的鞋墊,讓患者疼痛表達逐漸低於5以下,這代表研究中絕大多數患者(120名中的101名)經過長期使用青邊貽貝而被評為I級或II級。

青邊貽貝提取物作為一種安全有效的抗炎劑、免疫調節劑和軟骨再生的營養補充品,在治療膝關節炎的益處已被證明是可靠的。在這項研究中,許多患者顯著能夠減少他們的NSAIDs消炎藥的攝取量和止痛藥劑量,並使用每天1,000毫克的青邊貽貝維持更積極的生活方式。

Discussion of Results
The positive response of patients with gonarthrosis of the knee utilizing Perna mussel in this study was most encouraging. As a result, a modified approach to management of these patients in office practice has evolved. This overall approach is best expressed by the following algorithm. 
As mentioned, after the initial patient history and complete physical examination of including X-ray examination, all patients in this study were started on the Perna canaliculus regime. Most had been on NSAIDS and were allowed to continue. If not, they were started on an appropriate NSAID. If pain was expressed as above 5 on the visual analogue scale an intra-articular injection of cortisone was administered. In office practice it is important that the patient experience relief as soon as possible. All patients who were 5 and under on the visual pain analog scale were completely stabilized using Perna and appropriate shoe wedges. This represented the vast majority of the patients in the study (101 out of 120) who were rated as Grade I or Grade II. 
The benefits of the freeze-dried lyophilized Perna powder as a safe and effective anti-inflammatory agent, immune modulator and joint regenerative product in the office management of gonarthrosis has proven to be reliable. In this study a number of patients were significantly able to reduce their NSAID intake and pain medication dosage and maintain a more active lifestyle using a maintenance program of 1000 mg of Perna per day.


青邊貽貝已被證明在I級和II級骨關節炎的臨床評估中特別有效,而在II級患者中效果開始較差。它對IV級骨關節炎無效,其中骨損傷已經發展到硬骨上。在上面的證明中已經透過骨科醫生在關節病管理實務中,成為正規治療的替代方案。

一般而言,在實務中對膝關節炎的管理往往是現實的。關節炎被認為是慢性的和無法治癒的,這是由關節的“磨損”引起的老化的正常結果。醫生回憶起過去治療的目標“只能治癒一點,幫忙多些,然後安慰所有人” To cure a few, to help many, and to comfort all."。

但該研究表明骨關節炎是可逆的。I級和II級關節炎對使用青邊貽貝的非常明顯和持續的反應表現「軟骨具有天生的自我再生能力」。關節鏡檢查和10名患者的放射學證據強烈表明青邊貽貝有助於軟骨的重新生長。

Perna has been shown to be especially effective in this clinical evaluation for Grade I and II Osteoarthritis, and less effective in Grade II patients. It was not effective in Grade IV osteoarthritis where the damage had progressed to bone on bone. A possible alternative to orthodox therapy in the orthopedic management of gonarthrosis patients by a practicing orthopedist has been outlined in the algorithim above.
In general, management of arthritis of the knee in office practice tends to be realistic.Arthritis is considered to be chronic and incurable, a normal consequence of aging caused by "wear and tear" of joints. The physician does well to recall the traditional aim of treatment "To cure a few, to help many, and to comfort all." 
This study suggesta that osteoarthritis can be reversible. The very apparent and continued response of Grade I and II arthritis to the use of Perna mussel shows that cartilage has the innate ability to regenerate itself Arthroscopic and radiographic evidence on ten patients strongly suggests that Perna canaliculus contributed to new growth of cartilage. 

Hurley 博士的研究心得

軟骨不能癒合和自我修復的傳統教條可能是一種誤解。在這項研究之前,就有證據表示髖關節和膝關節手術的經驗,可以逆轉關節炎的改變。在本研究開始時有發表的論文是,在整形外科醫學的臨床實務中,導致骨關節炎的因素受到阻止並且有時會逆轉。

從本研究所包括的患者的日常主觀和客觀評價中收集的經驗顯示,這篇青邊貽貝逆轉關節炎的論文是可能的。從客觀的X射線和關節鏡的觀察中獲得的經驗表明了這一點。

引用上個世紀的威廉·奧斯勒爵士說:“這位年輕的醫生離開醫學院,為每種疾病服用了20種藥物,經過多年的經驗,他發現他對每種疾病有治療方法。”在過去的30年臨床經驗之後,過去十年中使用青邊貽貝以及常規的內科和外科治療,提醒了這一陳述的有效性之一。我現在開出抗炎藥、肌肉鬆弛藥和止痛藥的程度要小得多。

青邊貽貝也已被證明有助於控制運動損傷、骨折,尤其是老年骨質疏鬆女性的髖部骨折,以及一般的背部疼痛。具體而言,我對患有退化性椎間盤疾病和關節炎的患者所獲得的益處感到高興。鑑於椎間盤的蛋白多醣結構與關節軟骨的蛋白多醣結構差別很小,這是可以理解的。

對於禁止服用阿司匹林或阿司匹林類藥物的患者,青邊貽貝是一種很好的選擇,因為他們使用的是Coumadin,或因為預定的擇期手術而被要求停用這些藥物。由於相關的出血風險,我建議所有計劃手術的患者在手術前至少兩週停止所有NSAIDs。青邊貽貝已被證明具有接近Indocin 的抗發炎作用,並且在這些患者中產生了不同程度的控制。在選擇性整形外科手術之前準備好客戶,將青邊貽貝放在營養補充計劃上似乎是合理的。

Overview by Dr. Hurley 
The dogma that cartilage cannot heal and repair itself may be a misconception. Before this study there was evidence from experience with ostiotomy of the hip and of the knee that ostioarthritic changes could be reversed. The thesis developed at the beginning of this study was that the sequence of events resulting in osteoarthritis is subject to arrest and sometimes reversal, in the clinical office practice of orthopedic medicine. The experience gleaned from the day to day subjective and objective evaluation of patients included in this study suggests that this thesis is probable. The experience gained from the objective view of X-rays and from arthroscopic intervention suggests this.
 Sir William Osler at the turn of the last century is quoted saying "The young physician leaves medical school with twenty medications for each disease and after years of experience finds he has one remedy for 20 diseases." The use of Perna along with conventional medical and surgical therapy over the past ten years, following a previous 30 years of clinical experience reminds one of the validity of this statement. I now prescribe nonsteriodal anti- inflammatory drugs, as well aa muscle relaxants and pain medications to a much lesser degree. 
Perna canaliculus has proven to be helpftul in managing athletic injuries, fractures, particularly hip fractures in elderly osteoporotic females, and back pain in general Specifically, I have been pleased by the benefit obtained in patients afflicted with degenerative disk disease and facet arthrosis. This is understandable in view of the fact that the proteoglycan structure of the intervetebral disk differs very little from that of articular cartilage.
 Perna has been an excellent alternative for patients who are prohibited from taking aspirin or aspirin-like drugs because they are on Coumadin, or are required to discontinue these medications because of scheduled elective surgery. I advise all patients who are scheduled for surgery to discontinue all NSAIDS at least two weeks prior to surgery because of the associated risk of bleeding. Perna has been shown to have an anti- inflammatory effect approximating that of Indocin (carageenan assay) and has made a difference in these patients. It seems reasonable to prepare clients prior to elective orthopedic surgery by placing them on a nutritional supplement program that includes Perna canaliculus.

青邊貽貝的安全性,推薦用法和可能的協同作用
青邊貽貝提取物採用完整的冷凍乾燥方式提取,因此對大多數人來說是非常安全的,但那些對貝類過敏的人則不應該使用這種產品。即使在較高的使用水平下,該產品也不會對健康產生不良影響。有些人(不到10%)可能會因使用該產品而出現腸胃不適(消化不良或輕微噁心)。這可以與果汁、飲食搭配或使用較小劑量來改善。

有一些報告說,部分人在服用青邊貽貝幾天後,發現受損關節周圍的疼痛和溫度增加,這種輕微的不適通常在一到兩週後過去,並且可能表明該產品正在對關節本身起作用。在這段時間內服用鎮痛產品可能會有所幫助。重要的是要堅持使用該方案直至出現症狀緩解。根據病情的嚴重程度,病情的穩定可能需要一到三個月。


Safety, Recommended Usage and Possible Synergistic Effects of Perna 
 Perna is a whole, freeze-dried food derived from the green-lipped mussel and, as such, is perfectly safe for most people to consume. Those individuals with a shellfish allergy should not use this product. There are no adverse health effects from this product even at higher levels of consumption. Some people (less than 10 % ) may experience gastrointestinal upset (indigestion or slight nausea) from using the product .This can be reduced significantly by taking Perna with a meal, with juice or by taking smaller doses throughout the day. 
There have been a few reports that some people find increased tenderness and warmth around the afflicted joints after taking Perna for a few days. This mild discomfort usually passes after one to two weeks and may be an indicator that the product is working on the joint itself. Taking an analgesic product during this time period may be helpful.It is important to stayon the program until relief of symptoms occurs. Stabilization of the condition may take from one to three months depending on the severity of condition and the person's biochemical individuality.

根據臨床經驗,開始使用青邊貽貝的推薦方案是每天服用6粒膠囊(每粒500毫克,每日3,000毫克),每餐2粒膠囊的方式三餐服用,該劑量應遵循約一個月或直至病情或症狀改善。然後根據情況需要將劑量調整為每天2-4粒。在產品上經過三到六週後,通常會出現疼痛減輕、僵硬度降低和關節活動度增加的情況。

最近對狗的評估表明,當青邊貽貝與適當水平的硫酸葡萄糖胺和甲磺酸磺胺(MSM)結合時,可以看到更快和更有效的結果。目前正在進行一項研究,以評估將這三種軟骨保護劑組合成一種產品可能產生的協同效應。

Based on clinical experience, the recommended program for using Perna is to begin with 6 capsules (500 mg each) daily, 2 capsules with each meal. This dosage should be followed for approximately one month or until conditions or symptoms improve. Then the dose can be adjusted to 2-4 capsules daily as the situation warrants. A reduction in pain, reduced stiffness and greater joint mobility is generally experienced after three to six weeks on the product.
Recent evaluation in dogs indicate that when Perna canaliculus is combined with appropriate levels of Glucosamine Sulfate and Methyisulfonyimethane (MSM), faster and more effective results may be seen. A study is currently underway to evaluate the possible synergistic effect of combining these three chondo- protective agents into one product.


結論
動物和人類研究的持續研究繼續證明,使用整個青邊貽貝治療骨關節炎和類風濕性關節炎的安全有效。結果表明,青邊貽貝對I級和II級關節炎特別有效,其中該疾病未導致關節軟骨的嚴重損失。初步結果表明,青邊貽貝可有效減輕與該病症相關的疼痛和炎症,並促進關節軟骨的再生,從而在患者中產生更大的活動性和運動耐受性。 青邊貽貝控制促炎細胞因子並為結締組織(硫酸軟骨素,膠原蛋白和糖原)的重建提供多種營養因子的能力,可能有助於解釋這種來自海洋的天然產物的治療特性。目前正在進行的未來研究可以更好地理解青邊貽貝如何有效地用於抵抗其他炎症和自身免疫疾病,特別是當與其他已證實的軟骨保護劑結合使用時。

Conclusion 
Ongoing research in both animal and human studies continue to demonstrate that the use of the entire Perna canaliculus organism (not an extract) represents a safe and effective nutritional product for the management of osteoarthritis and rheumatoid arthritis. Results indicate that Perna is especially effective against Grade I and II arthritis where the disease has not led to major loss of the articular cartilage. Preliminary results indicate that Perna is effective in reducing the pain and inflammation associated with the condition as well as promoting regeneration of articular cartilage which results in greater mobility and exercise tolerance in the patient. The ability of Perna canaliculus to down regulate pro- inflammatory cytokines and provide a wide array of nutritional factors for the rebuilding of connective tissue (chondroitin sulfates, collagen and glycogen) may help explain the healing properties of this natural product from the sea. Future studies now underway may provide greater understanding on how Perna canaliculus can be used effectively against other inflammatory and autoimmue conditions,especially when combined with other proven chondroprotective agents.


註:青邊貽貝提取物

紐西蘭特有種青邊貽貝,提取出的成分中以 GAG 醣胺聚醣最為矚目,因為一般的葡萄糖胺(Glucosamine)經過食用後大約6~8週才能轉換成 GAG,成為關節可用的營養,但是青邊貽貝提取物穩定存在豐富的 GAG可直接被關節使用,當然青邊貽貝提取物中含有與人體相似的天然礦物質與其他成分也有助於關節炎的整體改善。

圖片來源 My Swiss Life

青邊貽貝在生長曲線的高峰期(大約18個月)收成,以急速冷凍乾燥的方式加工成細粉,這種方式不會破壞營養與活性,因此完整保存蛋白質、複合碳水化合物、脂質、天然礦物質、氨基酸和粘多醣(GAG 醣胺聚醣),為身體尤其是關節提供營養。符合潔淨海域、保存完整營養的青邊貽貝提取物,就會有「ORIGINAL PERNA EXTRAKT」的驗證標章。
圖片來源 My Swiss Life

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