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Friday, 11 December 2015

Most Common Diseases of elder: The Clinical Trials and Studies of Musculo-Skeletal disorders: Osteoporosis Treatment in Conventional Medicine Perspective

Kyle J. Norton (Scholar)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Musculoskeletal disorders (MSDs) are  medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. According to a community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home, musculoskeletal pain was reported by 57% of those interviewed(1).

      Types of Musculo-Skeletal disorders in elder(2)

1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia

                                Osteoporosis

Osteoporosis is defined as a condition of thinning of bone and bone tissues as a result of the loss of bone density over a long period of time. It is a widespread degenerative disease of skeletal joints and often associated with senescence in vertebrates due to excessive or abnormal mechanical loading of weight-bearing joints, arising from heavy long-term use or specific injuries(6).



                                The Treatments


A. In conventional medicine perspective
The osteoporosis Canada suggested the following treatment for patient with osteoporosis depending to differentiation(350).
A.1. Bisphosphonates
1. Including Alendronate (Fosamax), Risedronate (Actonel, Atelvia), Ibandronate (Boniva), Zoledronic acid (Reclast, Zometa), etc..Bisphosphonates are antiresorptive medications widely prescribed for treatment of osteoporosis. The drugs, used most common treatment for osteoporotic patients, regardless to intravenous and oral alendronate administration(351) have shown to significantly reduce the risk of osteoporotic fractures(356). Higher risk patients should be treated bynonbisphosphonate for 10 yr, have a holiday of no more than a year or two(353), but drug holidays should be considered for low-risk patients and in select patients at moderate risk of fracture after 3 to 5 years of therapy(352).
It is suggested that patient under treatment of bisphosphonates therapy should also diet with rich of calcium and vitamin D.

2. Side effects are not limit to
2.1. Nausea
2.2. Abdominal pain
2.3. Difficulty swallowing
2.4. Risk of an inflamed esophagus or esophageal ulcers(354) and Esophageal Cancer(357)
2.5. Fever, myalgias, and arthralgias(357)
2.6.  Musculoskeletal pain(357)
2.7. Hypocalcium(357)
2.8. Risk of sclerosis and a variety of ocular side effects(355)(357)
2.9. Atrial Fibrillation(357)
2.10. Severe Suppression of Bone Turnover(357)
2.11. Subtrochanteric Femoral Fractures

A.2. Hormone therapy
1. Hormone Therapy (HT) or estrogen/progesterone therapy, is commonly used to relieve the symptoms of menopause, especially for women in pre-menopause state with low lower progesterone-to-estrogen level of that induced more negative changes in bone (358). According to the, treatment with estrogen/progesterone in post menopause women showed a protective effect against significant changes in BMD and follow-up BMD(359) against loss of ovarian function due to aging induced increasing risk of osteoporosis(360).
 Estrogen/progesterone therapy with no intention to replace  the loss of these hormones due to post menopause, but to supplement these hormones to the lowest level required to prevent bone loss.

2. Hormone replacement therapy can help to maintain bone density for menopause women, but it increases
2.1. The risk of breast cancer and heart disease(361)
2.2. The risk for venous thromboembolism(362)
2.3. The risk of (Nonmelanoma Skin Cancers) NMSC.(363)
2.4. The risk of stroke(364)
2.5. Other side effects may also include arthralgia and mucosal dryness(365),

A.3. Estrogen replacement therapy
3.1.  Estrogen therapy HT, most used in menopausal women for relieving symptoms such as hot flash, night sweats, mood and sleep disturbances, vaginal dryness and pain with intercourse, insomnia or problems sleeping, frequent urination or urinary incontinence etc.(367).
 Estrogen production in women before menopause plays such an important role in maintaining bone density by balancing the bone turn over through stimulating the calcium absorption and serum vitamin D metabolites against osteoporosis(366). According to the Yale University study, low-dose estrogen therapy may be a better choice for prevention of osteoporosis in menopausal women due to its benefits of significant increased bone mineral density and reductions in markers of bone turnover with no increased risk of endometrial hyperplasia or other side effects(368).

3.2. Adverse effects
Side effects of estrogen replacement therapy are swelling of the ankles and legs, loss of appetite, weight changes, retention of water, nausea, vomiting, abdominal cramps, and feeling of bloatednes(369) and not limit to risk of breast cancer, liver cancer, stroke, gall-bladder disease, thromboembolism(370)(372), cardiovascular disease(371).

A.4. Bone Metabolism Regulator
4.1. Bone Metabolism Regulator including Osteoprotegerin (OPG) are types of human monoclonal antibody medicine used  to prevent RANKL-RANK interaction in bone metabolism through inhibiting osteoclast formation(376)(377), through their effects in reverses osteoporosis(376)(377).
Deficiency of Osteoprotegerin (OPG) reduce function of regulator of postnatal bone mass, decrease in total bone density and induced significant risk of osteoporosis(375).

4.2. Adverse effects of bone metabolism regulator are not limit to pain in the muscles, arms, legs or back and a skin condition with itching, redness and/or dryness. and to the risks of
arterial stiffness(373)(374) and cardiovascular diseases(373) such as atherosclerosis(374)

A.5.  Parathyroid hormone (PTH)
5.1. Parathyroid hormone (PTH) is a hormone released by the parathyroid gland with the function in raising levels of calcium in the blood stream.
In postmenopausal osteoporosis, abaloparatide, a human parathyroid hormone-related peptide analog increased BMD of the lumbar spine, femoral neck, and total hip in a dose-dependent manner, according to the study lead by the Harvard Medical School(378). Once-daily injections of parathyroid hormone have a prominat result in patient with osteoporosis, according to the research team lead by DR. Neer RM., decreased the risk of vertebral and nonvertebral fractures and increased vertebral, femoral, and total-body bone mineral density(379) as well as significantly improved BMD of lumbar spine, total hip, and femoral neck(380).

5.2. Adverse effects are not limit to dizziness, nausea and leg cramps and the risk of hypercalcemia, worsen secondary hyperparathyroidism (SHPT)(381), bone tumors(382).


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References
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(2) Musculoskeletal Disorders in the Elderly by Ramon Gheno, Juan M. Cepparo, Cristina E. Rosca,1 and Anne Cotten(PMC)
(3) Osteoporosis(Life extension)
(4) Hormone and bone by Francisco Bandeira1, Marise Lazaretti-Castro2, John P. Bilezikian3
(5) Growth hormone and bone by Ohlsson C1, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC.(PubMed)
(6) GH and bone--experimental and clinical studies by Isaksson OG1, Ohlsson C, Bengtsson BA, Johannsson G.(PubMed)
(350) Drug treatment(Osteoporosis Canada)
(351) A comparative study between intravenous and oral alendronate administration for the treatment of osteoporosis by Horikawa A1, Miyakoshi N2, Shimada Y2, Sugimura Y1, Kodama H1.(PubMed)
(352) Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays by Brown JP1, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, Goltzman D, Hanley DA, Hodsman A, Josse R, Jovaisas A, Juby A, Kaiser S, Karaplis A, Kendler D, Khan A, Ngui D, Olszynski W, Ste-Marie LG, Adachi J.(PubMed)
(353) Long-term use of bisphosphonates in osteoporosis by Watts NB1, Diab DL(PubMed)
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(357) Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays.
Brown JP1, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, Goltzman D, Hanley DA, Hodsman A, Josse R, Jovaisas A, Juby A, Kaiser S, Karaplis A, Kendler D, Khan A, Ngui D, Olszynski W, Ste-Marie LG, Adachi J.(PubMed)
(358) Negative spinal bone mineral density changes and subclinical ovulatory disturbances--prospective data in healthy premenopausal women with regular menstrual cycles.
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(359) Timing of follow-up densitometry in hormone replacement therapy users for optimal osteoporosis prevention by Checa MA1, Del Rio L, Rosales J, Nogués X, Vila J, Carreras R.(PubMed)
(360) Oral versus transdermal hormone replacement therapy by Stevenson JC1, Crook D, Godsland IF, Lees B, Whitehead MI.(PubMed)
(361) Ten reasons to be happy about hormone replacement therapy: a guide for patients by Studd J1.(PubMed)
(362) Hormone therapy and risk of venous thromboembolism among postmenopausal women by Canonico M1, Scarabin PY.(PubMed)
(363) Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer? by Birch-Johansen F1, Jensen A, Olesen AB, Christensen J, Tjønneland A, Kjær SK.(PubMed)
(364) Hormone therapy administration in postmenopausal women and risk of stroke by Renoux C1, Suissa S.(PubMed)
(365) Complementary medicine on side-effects of adjuvant hormone therapy in patients with breast cancer by Beuth J1, van Leendert R, Schneider B, Uhlenbruck G.(PubMed)
(366) Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis by Gallagher JC, Riggs BL, DeLuca HF.(PubMed)
(367) Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment by Rapkin AJ1.(PubMed)
(368) Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy by Richman S1, Edusa V, Fadiel A, Naftolin F.(PubMed)
(370) Adverse effects of estrogen therapy in a subset of women with ITP by Onel K, Bussel JB.(PubMed)
(371) Adverse effects during endocrine therapy for prostatic carcinoma with a high dose of estrogen by Shinkawa T, Ohfuji T, Osada Y, Ishisawa N.(PubMed)
(372) Oral contraceptives and menopausal hormone therapy: relative and attributable risks of cardiovascular disease,cancer, and other health outcomes by Bassuk SS1, Manson JE2.(PubMed)
(373) Bone metabolism regulators and arterial stiffness in postmenopausal women by Albu A1, Fodor D, Bondor C, Crăciun AM.(PubMed)
(374) Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease by Tousoulis D1, Siasos G, Maniatis K, Oikonomou E, Kioufis S, Zaromitidou M, Paraskevopoulos T, Michalea S, Kollia C, Miliou A, Kokkou E, Papavassiliou AG,Stefanadis C.(PubMed)
(375) osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification by Bucay N1, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS.(PubMed)
(376) Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis by Min H1, Morony S, Sarosi I, Dunstan CR, Capparelli C, Scully S, Van G, Kaufman S, Kostenuik PJ, Lacey DL, Boyle WJ, Simonet WS.(PubMed)
(377) Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption by Kostenuik PJ1, Shalhoub V.(PubMed)
(378) Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density inpostmenopausal women with osteoporosis by Leder BZ1, O'Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, Lyttle CR, Hattersley G.(PubMed)
(379) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis by Neer RM1, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH(PubMed)
(380) Single and combined use of human parathyroid hormone (PTH) (1-34) on areal bone mineral density (aBMD) inpostmenopausal women with osteoporosis: evidence based on 9  RCTs by Song J1, Jin Z1, Chang F1, Li L1, Su Y1.(PubMed)
(381) Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass by Chen CL1, Chen NC1, Liang HL1, Hsu CY1, Chou KJ1, Fang HC1, Lee PT1.(PubMed)
(382) MiR-125b inhibits stromal cell proliferation in giant cell tumor of bone by targeting parathyroid hormone 1 receptor by Wu PF1, Liang JY1, Yu F1, Zhou ZB1, Tang JY1, Li KH1(PubMed)