WHMC311. Session 24. Musculoskeletal System Disease Part 1. Naturopathic Medicine Department. Endeavour College of Natural Health endeavour.edu.

Transcription

1 WHMC311 Session 24 Musculoskeletal System Disease Part 1 Naturopathic Medicine Department Endeavour College of Natural Health endeavour.edu.au 1

2 Topic Overview o Overview of principles and considerations in herbal management of the musculoskeletal system. o Review anatomy and physiology of the musculoskeletal system. o Identify specific herbal medicines, drawing upon relevant literature, used in support and modulation of osteoarthritis, gout and osteoporosis o Discuss relevant drug interaction and potentiations Endeavour College of Natural Health endeavour.edu.au 2

3 Naturopathic Diagnostics (Jensen, 1952) Endeavour College of Natural Health endeavour.edu.au 3

4 Acute monoarthritis Joint Pain o Acute inflammation in a single previously healthy joint Causes: o Septic arthritis o Crystal synovitis o Monoarticular presentation of poly arthritis o Trauma o Haemarthrosis associated with clotting abnormality o Foreign body reaction Endeavour College of Natural Health endeavour.edu.au 4

5 Joint Pain Diagnosis o Age, sex, joint involved o Speed of onset, progress and duration o Associated periarticular inflammation o Other symptoms associated with pain (Wiley, 2005) Endeavour College of Natural Health endeavour.edu.au 5

6 Joint Pain Chronic inflammatory monoarthritis o Inflammatory monoarthritis that persists for more than 6 weeks Causes: o Foreign body o Infection o Chronic Sarcoidosis, Amyloidosis o Enteropathic arthritis o Pigmented villonodular synovitis Endeavour College of Natural Health endeavour.edu.au 6

7 Joint Pain Oligoarthritis o Arthritis affecting two, three or four joints or joint groups Causes: o Seronegative spondarthritis o Erythema nodosum o Juvenile idiopathic arthritis o Oligoarticular presentation of polyarthritis o infection Endeavour College of Natural Health endeavour.edu.au 7

8 Poly arthritis Joint Pain o Involvement of five or more joints or joint groups Causes: o Non inflammatory o Inflammatory Diagnosis: o Symmetrical or asymmetrical involvement o Involvement of upper or lower limbs o Involvement of large or small joints o Periarticular involvement Endeavour College of Natural Health endeavour.edu.au 8

9 Joint Pain Investigation and management o Blood tests o Liver function tests o Rheumatoid factor and antinuclear antibody o X ray Endeavour College of Natural Health endeavour.edu.au 9

10 Osteoarthritis Endeavour College of Natural Health endeavour.edu.au 10

11 Osteoarthritis o A condition of synovial joints characterised by focal loss of articular hyaline cartilage with proliferation of new bone and remodelling of joint contour. o Epidemiology o Aetiology and pathogenesis Cartilage changes Bone changes Other changes Endeavour College of Natural Health endeavour.edu.au 11

12 Osteoarthritis o OA is a condition of unknown aetiology but the most important factor is the ageing of connective tissue o Other implicated factors are An inherited predisposition Abnormal joint loading Biochemical abnormalities of cartilage Previous inflammatory joint disease Previous injury e.g. sporting injury (Kielczynski, 1997) Endeavour College of Natural Health endeavour.edu.au 12

13 Osteoarthritis Common symptoms: o Morning stiffness (relieved by movement) o Grinding of joints (crepitus) o Loss of mobility, range of movement o Pain after prolonged activity o Pain relieved by rest o Muscle contractures and spasms o In advanced OA, redness, heat, swelling, enlargement of joint, bone spur formation. (Rona, 2000) Endeavour College of Natural Health endeavour.edu.au 13

14 Osteoarthritis o It is probable that the joint structures reach the limit of their regenerative capacity earlier than other body tissues. o A number of environmental conditions, life circumstances, traumatic events, infections and other diseases and genetic factors might reduce the regenerative capacity even further. (Bone & Mills 2013, p ) Endeavour College of Natural Health endeavour.edu.au 14

15 Pharmaceutical Management There is no specific or disease-modifying orthodox therapy. Drug therapy revolves around symptomatic relief. Non-Opioid Analgesics Paracetamol (covered in session 5.2) o Inhibits prostaglandin production within the CNS providing analgesic and antipyretic properties. o Side Effects include skin rash and / or nausea. o Overdose will cause severe liver damage due to depletion of glutathione, and possibly lead to death. (Bryant & Knights, 2011; Bullock et.al. 2007) Endeavour College of Natural Health endeavour.edu.au 15

16 Pharmaceutical Management Anti-inflammatory Agents NSAIDs (covered in session 5.2) o Inhibit the synthesis & release of prostaglandins (COX-1 & COX-2) and platelet aggregation. o Side Effects include GIT irritation and skin reactions. Corticosteroids (intra-articular) o Inhibit phospholipase A & cyclo-oxygenase to reduce inflammation. (Bryant & Knights, 2011) o Side effects include pain &/ or infection at injection site, postinjection joint pain, tendon damage, loss of bone mass (long term therapy). (Bryant & Knights, 2011; Bullock et.al. 2007) Endeavour College of Natural Health endeavour.edu.au 16

17 o Alleviate the symptoms o Improve joint function Treatment Aims o Promote healing by Improving blood flow to the area o Identify and treat pain exacerbating factors Obesity Encourage activity which does not put extra strain on the affected joints Physical therapy to improve the mechanics of the joints by strengthening the appropriate muscles Use of functional aids (Orrock 2010, p.425) Endeavour College of Natural Health endeavour.edu.au 17

18 Treatment Aims o Herbal remedies are used to stop progression of the disease and permit regeneration of the cartilage by Increasing blood circulation into the affected area that binds cartilage to the bone Supplying carbohydrate molecules for proper proteoglycan synthesis and cartilage reconstruction Remineralisation of the highly calcified cartilage / bone junction Detoxification of joints by absorption of cartilage fragments, hydroxyapatite and calcium pyrophosphate. o Prompt attention is needed to prevent joint injuries (Bone & Mills 2013, p ) Endeavour College of Natural Health endeavour.edu.au 18

19 o As with skin diseases, arthritis is traditionally represented as toxic accumulation at the site. o With joints viewed as uniquely vulnerable structures, fairly obvious 'bottlenecks' in the circulatory flow (Bone & Mills 2013, p ) Traditional View Endeavour College of Natural Health endeavour.edu.au 19

20 Traditional View o It is widely understood that the body has to eliminate acid metabolites and that joint problems are a classic outcome of failure to do this. o Under such circumstances it makes sense to reduce acidic foods from the diet Not foods that taste acidic like citrus and other fruits But foods that leave an acidic residue after digestion, due to a preponderance of sulphates and phosphates. Proteins are the major example of this. One guide is to test the acidity of ash after combustion Endeavour College of Natural Health endeavour.edu.au 20

21 Herbal Actions o Analgesic o Antiarthritic o Antiinflammatory o Diuretic/ depurative o Circulatory stimulant o Rubifacient/Counter irritant o Spasmolytic o Nervine (Orrock 2010, pp ) Endeavour College of Natural Health endeavour.edu.au 21

22 Herbal Actions o The herbal diuretics can be understood as usefully complementing a high-alkali diet based on vegetables and fruits in reducing the rate of joint deterioration in many sufferers from osteoarthritis o The diuretic herbs may be augmented by inflammatory modulators traditionally used in arthritic disease (Orrock 2010, p434) Endeavour College of Natural Health endeavour.edu.au 22

23 Herbal Actions o Counterirritation is in a modern context explained as resulting from some form of stimulation of nerve receptors leading to reflex analgesia. o This does not do justice to the technique or to its therapeutic context Both rubefacients and blistering agents, expertly applied, are intrinsically comforting sensations. o Bone (2013) suggests that a better speculation might be that counterirritation is a pro-inflammatory technique. o With the increased vasoactivity and stimulation of other inflammatory mediators being seen as constituting a therapeutic inflammation, doing painlessly what the body itself does with pain, swelling and disability (Bone & Mills 2013, p ) Endeavour College of Natural Health endeavour.edu.au 23

24 Herbs to Consider o Salix alba (bark) o Harpagophytum procumbens o Boswellia carterii o Apium graveolens o Curcuma longa o Guaiacum Resin o Hypericum perforatum o Ginkgo biloba o Capsicum spp. o Actaea racemosa o Juniperus commuis o Zingiber officinalis o Zanthoxylum clavaherculis o Urtica dioca o Eschscholzia californica o Corydalis ambigua o Viburnum opulus o Valeriana officinalis (Mills & Bone, 2000, p.249) Endeavour College of Natural Health endeavour.edu.au 24

25 Capsicum minimum o Capsaicin from the fruit of Capsicum minimum and other species (cayenne) gives cayenne its spiciness. o Capsaicin is a powerful and basically safe tool for relieving a variety of forms of pain when applied topically. o However, since it does not treat the cause of pain, it must be seen as a supportive measure at best, and other efforts instituted whenever possible to eliminate the cause of the pain. (Yarnell, 2002) Endeavour College of Natural Health endeavour.edu.au 25

26 Capsicum minimum o Capsaicin has a unique mechanism of action. It binds to vanillinoid receptors and strongly promotes release of substance P, neurokinin, somatostatin, and calcitonin from peripheral nerve fibres, particularly C fibres in the slow pain network. This initially provokes worsening of pain and itching. However, with a few repeated applications, the C fibres are depleted of these neurotransmitters, and are no longer able to transmit pain or itch signals. With continued use, this effect can be sustained indefinitely. (Yarnell, 2002) Endeavour College of Natural Health endeavour.edu.au 26

27 o Actions Anti-inflammatory Analgesic Antirheumatic Antipyretic Salix alba o Dosage & Administration Clinical trial results suggest that mg/day of a suitably prepared willow bark extract should be administered (at a dosage containing to mg/day of salicin), with a pain relieving effect observed by the end of the first week for the high dosage and by the second week for the lower dosage (Bone & Morgan, 2002) Endeavour College of Natural Health endeavour.edu.au 27

28 Salix alba o Adverse Reactions Salicin, being a glycoside derived from salicyl alcohol, is less irritant to the mucous membranes than actual salicylates (salicylic acid derivatives). Unlike aspirin, willow bark extract is expected to have very mild effects on platelet function. o Contraindications & Cautions Willow bark is contraindicated in those with allergy or sensitivity to salicylates Use with caution during lactation as salicylates excreted in breast milk may cause rashes in babies. (Bone & Morgan, 2002) Endeavour College of Natural Health endeavour.edu.au 28

29 Harpagophytum procumbens Endeavour College of Natural Health endeavour.edu.au 29

30 Harpagophytum procumbens o In a large open study on 630 patients with various rheumatic illnesses 42% to 85% of patients showed significant improvement after 6 months of treatment with 3 to 9 g of the aqueous extract of Devil s Claw per day o The efficacy varied with the site of the arthritis, 80% of patients with arthritis in the large joints or spinal column experienced a significant improvement in symptoms whilst the remaining 20% experienced no therapeutic effect even at maximum dosage o However, one open study on 13 patients with rheumatoid arthritis and psoriatic arthropathy found no benefit from Devil s Claw treatment (Bone & Walker, 1997) Endeavour College of Natural Health endeavour.edu.au 30

31 Harpagophytum procumbens o Two double blind studies have also demonstrated the effectiveness of Devil s Claw as an antirheumatic agent. o In the first study improvements were more frequent in moderate cases than in the more severe cases of arthritis. o In the second the results indicated a significant drop in the intensity of pain and increases in spinal and coxofemoral mobility in the treated group. (Bone & Walker, 1997) Endeavour College of Natural Health endeavour.edu.au 31

32 Boswellia serrata o Actions Anti-inflammatory, antiarthritic. o Therapeutic Indications Conditions where leukotrienes play an important role as inflammatory mediators, such as inflammatory bowel disease, asthma, rheumatoid arthritis (RA) and psoriasis. Other inflammatory states characterized by elevated levels of leukotrienes include cystic fibrosis, allergic rhinitis, lupus, gout, urticaria, liver cirrhosis, multiple sclerosis and chronic smoking. May be of benefit for the local treatment of inflammation of the mouth and throat, as a gargle, (as are other resinous herbs from the same family e.g. Myrrh). May be useful in the treatment of hyperlipidaemia (Bone, 1999) Endeavour College of Natural Health endeavour.edu.au 32

33 Boswellia serrata o Dosage & Administration The dosage of Boswellia is 200 to 400 mg of extract three times a day. This extract should be standardised to have a boswellic acid content of about 60% and the dose corresponds to an equivalent resin intake of g Boswellia resin requires a high content of alcohol for extraction, similar to myrrh and guaiacum. For this reason, Boswellia is more conveniently dispensed as a tablet or capsule, given the relatively high doses required (Bone, 1999) Endeavour College of Natural Health endeavour.edu.au 33

34 Boswellia serrata o In an Indian trial with 75 patients suffering from mild to moderate OA a low dose extract of Boswellia was used over 90 days. o Corroborating the improvements in pain scores in treatment groups, there was also a markedly significant reduction in synovial fluid matrix metalloproteinase-3. o Boswellia has potential efficacy in terms of reducing pain and improving the physical ability of OA patients (Sengupta et.al.2008) Endeavour College of Natural Health endeavour.edu.au 34

35 Boswellia serrata o A significant improvement in symptoms was observed for 60 rheumatoid arthritis (RA) patients after receiving 6 to 8weeks of treatment with boswellic acids. o After reviewing the successful results of preclinical toxicology and efficacy studies, an uncontrolled clinical trial was undertaken at the orthopaedic department of Government Medical College, Jammu, India. o Results for 175 rheumatoid arthritis patients were excellent for 14% and good for 44%. o Most patients taking Boswellia had some improvement in symptoms such as pain, stiffness and poor grip strength. (Bone, 1999) Endeavour College of Natural Health endeavour.edu.au 35

36 Boswellia serrata o Fan et al (2005, p.104) conducted a random, blinded study, where the anti-arthritic effects of a Boswellia extract were observed and compared controls in a Lewis rat adjuvant arthritis model. o Arthritis was induced by injecting CFA subcutaneously into the base of the tail, and the extract was administered orally for 10 consecutive days beginning on day 16 after the injection. o The data show that Boswellia extract has significant antiarthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines. Endeavour College of Natural Health endeavour.edu.au 36

37 Apium graveolens o Common name: Celery seed. More correctly it is the celery fruit which is used o Actions Diuretic Antiinflammatory Antirheumatic (Bone, 2003, pp ) Endeavour College of Natural Health endeavour.edu.au 37

38 Apium graveolens o In an uncontrolled, preclinical trial in Australia, 15 patients with longstanding rheumatic pain received celery seed extract over 12 weeks. o The parameters measured were usual pain, current pain, and usual and current body areas experiencing pain. o Patients reported significant reduction in pain intensity for usual pain after weeks 3 and 6 and for current pain after weeks 3 and 12. o The number of joints at which pain was experienced was significantly decreased over each 3-week period (Bone 2003 pp ) Endeavour College of Natural Health endeavour.edu.au 38

39 Apium graveolens o A group of Egyptian scientists studied a number of plants used in folk medicine as diuretics. o The strongest diuretic found was the fruits of Anethum graveolens (Dill Seed). o Both the ethanolic extract and the essential oil of Dill Seed were active. o The essential oil was particularly potent, an injected dose of ml/kg in dogs produced an effect which lasted for more than 80 minutes. o The ethanolic extract of Apium graveolens fruit (Celery Seed) could not be studied because it produced a gelatinous material upon dissolving in saline. o The essential oil of Celery Seed was not active at lower doses and at higher doses produced a hypotensive response. (Bone 1992) Endeavour College of Natural Health endeavour.edu.au 39

40 Common name: Turmeric Curcuma longa Actions o Antiinflammatory o Antiplatelet o Antioxidant o Hypolipidemic o Choleretic o Antimicrobial o Carminative o Depurative (Bone, 2003, pp ) Endeavour College of Natural Health endeavour.edu.au 40

41 Curcuma longa o In a randomised, double-blind, placebo-controlled, crossover trial, patients with osteoarthritis received a preparation containing Turmeric, Withania, Boswellia, and a zinc complex or placebo for 3 months. o Treatment with the herbal-mineral preparation produced a significant drop in severity of pain and disability (Bone, 2003, pp ) Endeavour College of Natural Health endeavour.edu.au 41

42 Curcuma longa o The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. o Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors, enzymes, cell cycle proteins, cytokines, receptors, and cell surface adhesion molecules (Shishodia et al, 2005) Endeavour College of Natural Health endeavour.edu.au 42

43 Curcuma longa o Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. o The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots. (Shishodia et al, 2005) Endeavour College of Natural Health endeavour.edu.au 43

44 Curcuma longa o Studies by Funk et.al.(2006, p4) showed that in vitro biological screening PGE2 assay suggested that purified curcuminoids could be 10-fold less potent as antiinflammatories while their in vivo studies demonstrated the exact opposite with respect to its efficacy as an antiarthritic. o They stated nil awareness of any studies in animals or humans which investigated the use of turmeric products for the treatment or prevention of other types of arthritis. Endeavour College of Natural Health endeavour.edu.au 44

45 Zingiber officinale Endeavour College of Natural Health endeavour.edu.au 45

46 Zingiber officinale o In 2007, 10 patients with OA were treated using Ginger compresses and it was found that there was a constant penetrating warmth throughout the body, overall improved sense of well-being. The patients also found an increased suppleness within the body and more comfortable, flexible joint mobility (Therkelsen 2010,p 2225). o Therkelsen states the essential experience of ginger compresses exposed the unique qualities of heat, stimulation, anti-inflammation and analgesia. Endeavour College of Natural Health endeavour.edu.au 46

47 Zingiber officinale o In 2001, Altman & Marcussen carried out a randomised, double-blind, placebo-controlled, multicentre, parallelgroup, 6-week study on 261 patients with OA of the knee and moderate-to-severe pain. After washout, patients received ginger extract or placebo twice daily, with acetaminophen allowed as rescue medication. o Conclusion: A highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of OA of the knee. This effect was moderate. There was a good safety profile, with mostly mild GI adverse events in the ginger extract group. Endeavour College of Natural Health endeavour.edu.au 47

48 Zingiber officinale o According to the Commission E monographs Ginger is contraindicated in patients with gallstones except in consultation with a doctor (1998, p136). o Its use in pregnancy has not been fully approved. It should be used under expert supervision despite it being one of the most used over the counter herbs for morning sickness (Mills & Bone 2005, p420). o Doses of dry weight 2g or more needs be used with caution in patients using anticoagulants. Patients with bleeding disorders need to seek doctor s advice (Mills & Bone 2005, p423). Endeavour College of Natural Health endeavour.edu.au 48

49 Urtica dioica Endeavour College of Natural Health endeavour.edu.au 49

50 Urtica dioica o Nettle leaves (Urtica dioica and Urtica urens) have traditionally been used orally and topically as adjuvant therapy for rheumatic disease. o In 1987, the German Commission E, supported this usage with a positive monograph. o A group of German scientists carried out a series of in vitro tests, in order to understand the anti-inflammatory potential of Nettle leaves (Bone, ND) Endeavour College of Natural Health endeavour.edu.au 50

51 Drug - Herb Interactions NSAIDs - Aspirin Capsaicin o Found to protect gastric mucosa against aspirin-induced damage. (Braun & Cohen, 2010) Grapeseed extract o Enhances antiplatelet and anti-inflammatory activity of aspirin and may risk of bleeding. (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 51

52 Drug - Herb Interactions NSAIDs Zingiber officinalis and Curcuma longa o Inhibits COX & LOX pathways therefore enhancing the drug effectiveness. Additive effect. (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 52

53 Gout Endeavour College of Natural Health endeavour.edu.au 53

54 Gout o An arthritic disease caused by accumulation of urate crystals at joints. o Not all individuals with very high serum urate levels will develop gout. o Medical treatment consists of Allopurinol which is a potent inhibitor of xanthine oxidase and very effective. o Acute gout needs to be treated cautiously as a sudden lowering of blood urate levels by treatment may prolong an attack. o If the individuals are overweight, then gradual weight loss is required, as the lactic acidosis associated with severe calorie restriction can raise blood urate levels (Mills & Bone 2000, p250) Endeavour College of Natural Health endeavour.edu.au 54

55 Gout Aetiology o Primary gout o Secondary gout Uric acid crystals o Factors that predispose to chronic hyperuricaemia and gout Clinical features o Acute gout o Recurrent and chronic gout o Chronic tophaceous gout o Renal and urinary tract manifestations Endeavour College of Natural Health endeavour.edu.au 55

56 Pharmaceutical Management Xanthine Oxidase Inhibitor Allopurinol Mode of Action o Reduces the synthesis of uric acid by inhibiting the action of xanthine oxidase. This increases xanthine s use in nucleic acid synthesis which in turn inhibits purine synthesis. Useful for urate deposits in the joints & urate kidney stone formation Side Effects o Skin irritation (itch, rash, dermatitis, alopecia) o abdominal irritation (diarrhoea, vomiting) o Liver toxicity, kidney damage (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 56

57 Pharmaceutical Management Colchicine Mode of Action o Plant alkaloid used in the acute attacks to reduce inflammation and. Has no preventative effect. Side Effects o Diarrhoea, nausea, vomiting, abdominal pain, anorexia & alopecia (long term use) o Narrow therapeutic window used with caution in individuals with liver or kidney impairment (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 57

58 Pharmaceutical Management Probenecid Mode of Action o Competitively inhibits urate reabsorption in the kidneys, increasing excretion. Side Effects o Headaches o Abdominal irritation (anorexia, nausea, vomiting) o Skin irritation (dermatitis) o Kidney irritation (haematuria, increased frequency, stone formation, kidney damage) o Anaemia, leukopenia (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 58

59 Pharmaceutical Management Anti-inflammatory Agents NSAIDs & Corticosteroids (intra-articular) o Utilised for symptomatic relief of pain and inflammation. o These are not as prophylactic agents. (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 59

60 Treatment Considerations o There are a number of herbs which are claimed to increase elimination of urates from the kidneys particularly Apium graveolens (Celery) Urtica dioica (Nettle leaf) o Prescriptions based on such herbs appear to ease the symptom, and even help to prevent recurrence. (Orrock 2010,235) Endeavour College of Natural Health endeavour.edu.au 60

61 Treatment Considerations o Uric acid is also excreted via the liver, and choleretic herbs are indicated to improve bile production Taraxacum officinale Cynara scolymus o Herbs containing significant amounts of salicylates are best avoided as they may inhibit uric acid excretion Salix alba Filipendula ulmaria (Mills & Bone, 2013, p ) Endeavour College of Natural Health endeavour.edu.au 61

62 Dietary Recommendations o Eat low purine foods (yeast, shellfish, organ meats & offal) o Eliminate refined sugar in drinks & food o Avoid coffee and caffeine consumption (Jasvinder et al. 2010) o Eliminate alcohol consumption o Reducing an unhealthy waist-to-height independent of body mass index o Increase fibre, folate and vitamin C rich foods (Lyu et al. 2003) o Increase filtered water to 2 litres /day o Increase consumption of essential fatty acids(pizzorno & Murray, 2006) Endeavour College of Natural Health endeavour.edu.au 62

63 Osteoporosis Endeavour College of Natural Health endeavour.edu.au 63

64 Osteoporosis o Disease of bone leading to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced, bone micro architecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. o Clinical features: Fragile fractures, back pain, height loss and kyphosis o Management o Biphosphates o Hormone replacement therapy (Trickey 2011, pp ,502) Endeavour College of Natural Health endeavour.edu.au 64

65 Pharmaceutical Management Bisphosphonates Alendronate Mode of Action o Bind to bone hydroxyapatite crystals, becoming a permanent part of bone. This new matrix is resistant to enzymatic degradation and inhibits osteoclast activity. Side Effects o Gastrointestinal irritation (dyspepsia, nausea, vomiting, oesophageal irritation, gastritis, abdominal pain, diarrhoea) o Osteomalacia, hypocalcaemia o Musculoskeletal pain, arthralgia, headache (Bryant & Knights, 2011; Bullock et al. 2007) Endeavour College of Natural Health endeavour.edu.au 65

66 Pharmaceutical Management Calcitonin Mode of Action o Thyroid hormone that inhibits osteoclast bone resorption by blocking the PTH action on these cells. Most effective in early menopause. Side Effects o Gastrointestinal upset (nausea, vomiting) o Dizziness o Inflammation and pain at injection site (Bullock et al. 2007; Mahan & Escott-Stump, 2008) Endeavour College of Natural Health endeavour.edu.au 66

67 Pharmaceutical Management Hormone Replacement Therapy Mode of Action o Oestrogen reduces bone turnover, bone loss, increases calcium absorption, calcium retention and increases calcitriol concentrations. o HRT provides low dose synthetic oestrogen (commonly combined with progesterone) when there is reduced endogenous production. Side Effects o Increased risk of coronary heart disease, breast cancer, stroke and pulmonary embolism (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 67

68 Pharmaceutical Management Selective Oestrogen Receptor Modulators Raloxifene, Tamoxifen Mode of Action o Stimulate oestrogen receptors in bone tissue without stimulating glandular tissue. These drugs have been shown to decrease bone resorption and increase bone mineral density. Side Effects o Hot flushes (usually subsides after 6 months) & leg cramps are common effects. o retinal vascular occlusion (Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 68

69 Pharmaceutical Management Androgen Replacement Therapy Mode of Action o Testosterone replacement helps to maintain bone mass and prevent fractures. Side Effects o Prostate growth (Mahan & Escott-Stump, 2008) Endeavour College of Natural Health endeavour.edu.au 69

70 Treatment Considerations o Phytoestrogen therapy may offer a limited protective role o Reduce systemic inflammation o Reduce risk factors such as overweight Suggested herbs: o Actaea racemosa o Cinnamomum zeylanicum was shown to inhibit osteoclastogenesis (Tsuji-Naito 2008 as cited in Trickey 2011, p511) o In another study Ganoderma lucidum was found to have a bone-protective effect (Myamoto et.al.2009 as cited in Trickey 2011,p511). Endeavour College of Natural Health endeavour.edu.au 70

71 Phytoestrogens in Osteoporosis o Study conducted to determine the effects of dietary inclusion of soy foods on clinical markers for cardiovascular disease (CVD) and osteoporosis in normal postmenopausal women. The conclusion was that dietary soy foods containing 60mg/day of isoflavones results in significant increases in serum levels of phytoestrogens and a subsequent reduction in clinical risk factors for CVD and osteoporosis. (Scheiber, 2001) o In addition, many other studies have shown the benefits of phytooestrogens in both management of menopause and prevention of osteoporosis Endeavour College of Natural Health endeavour.edu.au 71

72 Phytoestrogens in Osteoporosis o Based on promising results with dietary phytoestrogens and data from small scale studies with synthetic isoflavones. o A trial was conducted to investigate the effect of oral ipriflavone (a synthetic isoflavone) on the prevention of bone loss in postmenopausal women and to assess the safety profile of ipriflavone. o Randomised, double-blind, placebo-controlled, study conducted over 4 years in 4 different European centres. The study included 474 postmenopausal women between the ages of with BMDs of < 0.86g/cm2. (Alexandersen et al, 2001) Endeavour College of Natural Health endeavour.edu.au 72

73 Phytoestrogens in Osteoporosis o The patients were randomized to receive ipriflavone 200mg three times a day or placebo. All received calcium 500mg / day. The calcium salt used was not specified. All the women in trial had a body mass index of > 30kg/m2. o The results of the trial indicated that ipriflavone did not prevent bone loss or affect biochemical markers of bone metabolism. Additionally, ipriflavone induces lymphocytopenia in a significant number of women. (Alexandersen et al, 2001) Endeavour College of Natural Health endeavour.edu.au 73

74 Drug Herb Interactions Hormone Replacement Therapy Selective Oestrogen Receptor Modulators Actaea racemosa, Humulus lupulus, Trifolium pratense o Due to the oestrogenic activity of these herbs, effectiveness of the drug may be compromised. Glycyrrhiza glabra o Increased side effects due to the potassium depleting effect of this herb Hypericum perforatum o Due to CYP induction serum drug levels may be diminished (Stargrove et al. 2008; Braun & Cohen, 2010) Endeavour College of Natural Health endeavour.edu.au 74

75 Pre-reading for next session o Reading 1: Qui, SX Dan, C Ding, LS Peng, S Chen, SN Farnsworth, NR Nolta, J Gross, ML & Zhou, P 2007, A Triterpene Glycoside from Black Cohosh that Inhibits Osteoclastogenesis by Modulating RANKL and TNFa Signaling Pathways Chemistry & Biology, vol. 14, no. 7, pp o Reading 2: Belcaro, G Cesarone, MR Dugall, M Pellegrini, L & Ledda, A 2010, Efficacy and Safety of Meriva, a Curcuminphosphatidylcholine Complex, during Extended Administration in Osteoarthritis Patients Alternative Medicine Review, vol. 15, no. 4, pp Endeavour College of Natural Health endeavour.edu.au 75

76 Pictures: References Anatomy: Davidson s Principles and Practice of Medicine, 21 st edn, Churchill Livingstone, Edinburgh Text: Ahmed, S, Anuntiyo,J, Malemud,C.J, and Tariq M. Haqqi T.M, 2005, Biological Basis for the Use of Botanicals in Osteoarthritis and Rheumatoid Arthritis: A Review, Evidence Based Complementary & Alternative Medicine. September; 2(3): doi: /ecam/neh117. PMCID: PMC Alexandersen P et al Ipriflavone in the Treatment of Postmenopausal Osteoporosis: a Randomized Controlled Trial. JAMA. 285 (11): Altman RD, Marcussen KC, 2001, Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis & Rheumatism, Nov, Vol 44, Issue 11, pp Avery s Drug Treatment 4 th Edition Adis International Bone, K 1999, Boswellia serrata Boswellia, Professional Review, No.69, pp.1-4. Bone, K 2004, Masters course lecture notes, University of New England, Armidale. Bone K., & Morgan M., 2002, Willow Bark: High Potency Extract, Professional Review, No.78, pp.1-4 Bone K., & Walker M., 1997, Devil s Claw A Herbal Antiarthritic? Part 1, Professional Review, No.55. Bone K., 2003, A Clinical Guide to Blending Liquid Herbs, Churchill Livingston, pp Bone K., 1992, Herbal Diuretics studied, Professional Monitor No.1, p.2. Bone K., 2003, A Clinical Guide to Blending Liquid Herbs, Churchill Livingston, pp Bone K., 1996, Ginger The Herbal Aspirin? Part 2, Professional Monitor, No.53. Bone K., Nettles for Arthritis? Professional Monitor, No.22 Bone, K Mills, S 2013, Principles and Practice of Phytotherapy, 2 nd Edn. Churchill Livingston, Edinburgh Braun L, Cohen M Herbs and Natural Supplements, An Evidence-based Guide (3rd Ed), Churchill Livingstone Elsevier. Endeavour College of Natural Health endeavour.edu.au 76

77 References Braun L, Cohen M Herbs and Natural Supplements, An Evidence-based Guide 2 nd Edition. Churchill Livingstone Elsevier Bryant B & Knights K 2O11, Pharmacology for Health Professionals. 3 RD ed. Mosby Elsevier Australia Bullock, S Manias, E & Galbriath, A 2007, Fundamentals of pharmacology. 5 th ed. Pearson, NSW. Di Piro JT et al Pharmacotherapy, A Pathophysiological Approach (3rd Edition). Appelton Lange USA Fan AY, Lao L, Zhang RX, Zhou AN, Wang LB, Moudgil KD, Lee DY, Ma ZZ, Zhang WY, Berman BM. 2005, Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats, Journal of Ethnopharmacology, Vol.101, No.1-3, pp Funk J.L, Oyarzo J.N,Frye,J.B, Chen,G, Lantz,R.C, Jolad,S.D, Sólyom,A.M, Timmermann, B.N, Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis Journal of Natural Products. March; 69(3): doi: /np050327j. PMCID: PMC NIHMSID: NIHMS Goodman and Gilman The Pharmacological Basis of Therapeutics (9th Edition). McGraw-Hill Jensen, B 1952, The Science and Practice of Iridology Vol.I & Vol.II, Jensen Publishers, USA Kielczynski V., 1997, Osteoarthritis Clinical Outcomes After Uniform, Long-Term Herbal Treatment, Modern Phytotherapist, Vol.3, No.2, pp.1-7 Lyu, L Hsu, C Yeh, C Lee, M Huang S & Chen, C 2003, A case-control study of the association of diet and obesity with gout in Taiwan. American Journal of Clinical Nutrition, Vol. 78, No. 4, pp Mahan LK & Escott-Stump, S 2008, Krause s food and nutrition therapy. Saunders Elsevier, Missouri. Mills, S & Bone, K 2000, Principals and Practice of Phytotherapy, Churchill Livingston Mills S, Bone K The Essential Guide to Herbal Safety. Elsevier Churchill Livingstone. MIMS Desk Reference April/May 2006 Orrock P, 2010, Osteoarthritis in Sarris J, Wardle J, 2010(eds), Clinical Naturopathy. An evidence-based guide to practice. Churchill Livingstone Elsevier Endeavour College of Natural Health endeavour.edu.au 77

78 References Pizzorno JE, Murray MT 2006, Textbook of Natural Medicine. 3 rd ed. Churchill Livingstone, Edinburgh Rona, Z. 2000, Osteoarthritis, Alive Books, Barnaby. Shishodia S, Sethi G, Aggarwal BB, 2005, Curcumin: getting back to the roots, Annuals of the New York Academy of Science, Vol.1056, pp Stewart KM, Cole D. 2005, The commercial harvest of devil's claw (Harpagophytum spp.) in southern Africa: the devil's in the details. Journal of Ethnopharmacology, Vol.100, No.3, pp Scheiber, MD et al Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause. Vol 8(5): Sengupta,K Alluri,K.V, Rama Satish A, Mishra S, Golakoti T, VS K Sarma, Dey D, Raychaudhuri S.P.2008, A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee, Arthritis Research & Therapy.; 10(4): R85. Published online 2008 July 30. doi: /ar2461. PMCID: PMC25756 Stargrove, MB Treasure, J & McKee, DL 2008 Herb, nutrient, and drug interactions. Clinical implications and therapeutic strategies. Mosby Elsevier, Missouri. The Merck Manual 17th Ed. 1999, Merck Research Laboratories, N.J., USA. Therkelsen T,2010, Ginger compress therapy for adults with osteoarthritis, Journal of Advanced Nursing October; 66(10): doi: /j x. PMCID: PMC Trickey, R rd Ed. Women, Hormones & the Menstrual Cycle, Trickey Enterprises, VIC, Australia. Yarnell E., 2002, Phytotherapy for the Treatment of Pain, Modern Phytotherapist, Vol.6, No.3, p8. Yarnell E., 2002, Phytotherapy for the treatment of pain, Modern Phytotherapist, Vol.6, No.3, p8 Endeavour College of Natural Health endeavour.edu.au 78