Wednesday, 2 December 2015

Most Common Diseases of elder: The Clinical Trials and Studies of Musculo-Skeletal disorders: Osteoporosis - The diseases associated to Osteoporosis

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 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 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 diseases associated to Osteoporosis

Misdiagnosis of osteoporosis is rare, but it can happen in comprised with misdiagnosis with diseases.

1. Haemochromatosis
Hemochromatosis is a genetic defect of gene (C282YY) and a compound heterozygous mutation (C282Y/H63D)(143). Patient with the disease is associated to risk of 25% of osteoporosis and 41% of osteopenia(144). Patient with osteoporosis-hemochromatosis with misdiagnosis(146) and delay diagnosis(147) of hemochromatosis can induce complications of liver cirrhosis and carcinoma, diabetes or heart failure(145).

2. Myeloma
Multiple myeloma (Myeloma) is a type of cancer originated from plasma cells in the bone marrow induced symptoms of bone pain, infection, anemia, bleeding, back pain certain neurological symptoms, etc.,..(148). 
In the United States, each year approximately 700,000 vertebral body compression fractures due to osteoporosis and bone metastasis
with approximately 70,000 of these resulting in hospitalization(151). Clinical manifestations of multiple myeloma may be derived directly from the malignant infiltration of bone marrow associated to osteoporosis(149), through alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, inducing skeletal destruction(150).
According to the Homerton University Hospital, the coexistent osteoporosis and multiple myeloma can induce multiple vertebral fractures in the context of severe osteoporosis causes of vertebral collapse fracture(152).

3. Wilson's Disease 
Wilson's Disease is a genetic disease causes of disorder of copper metabolism(excessive amounts of copper accumulate in the body, especially in the liver and central nervous system). The high prevalence of the osteoporosis in patient with Wilson's diseases(154) may lead to fractures(155) and lower bone mineral density (BMD)(155) due to bone loss,...Patient with WD comprised of severe neurological involvement, low BMI, and/or amenorrhea ate found to associate to risk of fracture, probably due to lower bone mineral density(153)

4. Crohn's disease 
Crohn's disease  is a chronic inflammatory bowel diseases associated to the intestine(156). Patients with inflammatory bowel disease(IBD) are found to associate to metabolic bone diseases such as osteopenia and osteoporosis, a study in Japan insisted(157). In a cross-sectional study of 388 patients with IBD aged 20-50 years, lower bone mineral density, including  mineral density of the femoral neck, total femur and lumbar spine is coexiated in patient with Crohn's disease(158). The study of Iranian patient, risk of developing osteopenia and osteoporosis increase in patient of Crohn's diseases with smoking, corticosteroid use, age, and BMI(159).

5. Kidney disease
Kidney disease is a chronic disease with gradual loss of renal function over a prolonged period of time. Lifestyle-related diseases, including chronic kidney disease have been shown to have a possible effect on bone metabolism of which can lead to decrease in bone mineral density and an increase risk of fracture(160)(161). According to Capital Medical University Beijing, osteoporosis biomarkers in some case can act as predictors for diagnosis of chronic renal insufficiency in elder patients(162). Patient with pyperparathyroidism due to renal insufficiency may lead to turbulence of bone metabolism and unbalance between serum calcium and phosphorus(162). Renal osteodystrophy damage of bone morphology and abnormal bone metabolism by CKD due to P and Ca abnormalization of mineral metabolism(163).

6. Lupus
 Lupus, is an immune disorder disease causes of chronic inflammation associated to the attack of immune system against its won tissues(164). Osteoporosis is considered as a long term complication of patient with lupus due to its effect in reduced quality of life, increased mortality rates and increased risk of new vertebral and non-vertebral fractures(165). According to the University of Birmingham, in a cross sectional study of a large cohort of patients with systemic lupus erythematosus (SLE), the prevalence of reduced bone mineral density (BMD) and fractures, and risk factors for fractures were significantly high(166). According to Medicines that May Cause Bone Loss, patient with lupus may need to take medicines, including steroids, to control their symptoms of which can cause bone loss and osteoporosis(167).

7. Multiple sclerosis(MS)
Multiple sclerosis, is an immune disorder associated to demyelinating disease of the central nervous system due to the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies by the immune system(168). Patient with MS have found to at risk of low bone mineral density and fracture(170). According to Kings College London, used of glucocorticoid for treatment of MS although reduced mobility but increased risk for osteoporosis(169). The University Hospital of North Norway study suggested that due to high prevalence of osteoporosis in patients with multiple sclerosis and the share of aetiological risk factors such as smoking and hypovitaminosis D, as well as pathogenetic players such as osteopontin and osteoprotegerin, BMD should be measured shortly after diagnosis(171).

8. Ankylosing spondylitis(AS)
Ankylosing spondylitis, a type of spinal arthritis, is an inflammatory disease affected your spine. According to the study of 204 patients with AS by University of Gothenburg and 55 AS patients and 33 healthy controls by Izmir Tepecik Training and Research Hospital elevated serum levels of Wingless protein(Wnt-3a) and low levels of osteoprotegerin (OPG) may be used as biomarkers of bone metabolism in relation to osteoproliferation and osteoporosis(172)(173) respectively.
The Cochin Hospital study insisted that both AS and osteoporosis related to both systemic inflammation and decreased mobility and vertebral fracture risk(174), but so far there are no effective treatment in decreased risk of fractures(174)

9. Celiac Disease(CD)
Celiac Disease, is an multisystem autoimmune disorder in which such the disgestive system is highly sensitive to gluten Celiac disease. Patient with CD may experience secondary osteoporosis of that can lead metabolic osteopathy and joint and muscle problems and risk fracture(176),due to abnormal bone mineral metabolism (total calcium/albumin, 25-OH vitamin D3 and parathormone levels in serum) and bone mineral density (densitometry)(175).
According to the Hacettepe University, in the study of 34 children with untreated celiac disease at diagnosis and in 28 patients on a gluten-free diet, suggested that early diagnosis and treatment of celiac disease during childhood with a strict gluten-free diet improves bone mineralization and against the devopment of osteoporosis(177).

10. Diabetes
Patient with diabetes have a higher risk of developing osteoporosis. Indeed, osteoporosis and its related fractures, are clinically significant and commonly problem in diabetes type I and II patients(181). An India study of a prospective cross-sectional study on 150 patients with T2DM showed that patient with type 2 diabetes have significantly lower BMD at both femoral neck and lumbar spine compared to age and sex matched healthy controls(178). Postmenopausal women with non-insulin dependent type 2 diabetes mellitus (T2DM) also have an increased risk of osteoporosis(180) and vitamin D deficiency(179).

11. Hyperparathyroidism
Hyperparathyroidism is a medical condition of excessive serum of thyroid hormones in the blood stream induced a variable degree of osteopenia(184). Patient with the disease is at the greater risk of in developed osteoporosis and and fractures, especially in the population of in the young and in the early postmenopausal period, according to the La Sapienza University, but have a protective effect on trabecular bone in elderly postmenopausal women(182).
The study by Queen's University, Kingston, found that the alternation of vitamin D in these patient may lead to the development of secondary hyperparathyroidism in primary osteoporosis and osteopenia(183)

12. Hyperthyroidism

Hyperthyroidism is a medical condition of over production of thyroid hormone by the thyroid glands. Patient with hyperthyroidism, including subclinical hyperthyroid is at increased rate to risk of osteoporosis(185)(188) of which can lead to reduce in bone resorption and in ossified bone mineral deposition(185). In thyrotoxicosis patients with Graves' disease, according to the Yokohama Rosai Hospital, the resorption and formation was imbalance may result of decreased bone mineral density (BMD) and increased risk for osteoporotic fracture(186). Dr. Sato K. said" ...the gradual decrease in bone mineral density (BMD),..... In young patients, the decreased BMD is reversible, but not in post-menopausal women"(187)

13. Cushing’s syndrome
Cushing’s syndrome is a medical condition of over production of corticosteroid hormones (hypercortisolism) by the adrenal cortex of that can lead to higher risk of osteoporosis of that can induce further fractures and bone loss(189). Glucocorticoid therapy used mostly for treatment of the disease may elaborate the impaired the replication, differentiation and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes(190)(191). Dr. Suzuki Y. said" for management of GC-induced osteoporosis,....alendronate and risedronate are recommended as first-line treatment. Ibandronate, teriparatide, and active vitamin D3 derivatives are recommended as alternative option...."(192).

14. Leukemia and Lymphoma
Leukemia is defined as condition of abnormal increase of white blood cells produced by the bone marrow and/or the lymphatic system(193). According to the study by the University of Ottawa, increased odds for fracture, reduced lumbar spine (LS) and bone mineral density(BMD) as a result of vertebral compression, a serious complication of childhood acute lymphoblastic leukemia (ALL)(195).
Lymphoma is defined as a condition of cancer in the lymphatic cells (lymphocytes) of the immune system originated in lymph nodes. It represents a group of over 20 types of cancers(194).
According to the John Radcliffe Hospital, lymphomas share some common pathological and clinical features with multiple myeloma (MM), including the association with osteoporosis(198), such as correlating serum levels of osteoclast activating cytokine(198)
Chemotherapy used for treatment of leukemia and lymphoma is associated to high rate of osteoporosis and osteopenia(196)(197).

15. Sickle Cell Disease(SCD)

Sickle Cell Disease is a severe case genetic disorder of anemia caused by mutation of hemoglobin in the red blood cells, afflicting the oxygen absorption. Children with sickle cell anemia is associated to risk of lower bone mineral density(199). In adult with with SCD, the prevalence of abnormal bone mass density (BMD) is high (60%) with a significant low serum level of vitamin D3 and low testosterone hormone in those with very low bone mass density (BMD)(200). Dr,.Patil PL and Dr. Rao BV. said" Early diagnosis of this disease by family physicians will enable initiation of therapy..........patients education regarding management of modifiable risk factors linked with osteoporosis"(201).

15. Thalassemia
Thalassemia, also known as Mediterranean anemia, is a mild form of genetic blood disorder affecting the formation of hemoglobin. 
 There are strong evidence and indication of the association among children, adolescents and young adults with thalassaemia major (TM) in the development of the osteopenia/osteoporosis of that can induce the skeletal abnormalities, fractures, spinal deformities, nerve compression and growth failure, if the diagnosis is delay(202). The diseases is found to contribute to seriously diminished bone mineral density (BMD) as a result of an unbalanced bone turnover with an increased resorptive phase(203).
In fact, Osteopenia-osteoporosis syndrome (OOS) have shown to affect over 60-80% β-thalassemia major (β-TM) patients(204), according to the University College London Hospitals. 

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(201) Sickle cell disease with osteogenesis imperfecta by Patil PL, Rao BV.(PubMed)

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