Musculo-Skeletal Disorders - Osteoporosis

7/30/2019 Musculo-Skeletal Disorders - Osteoporosis

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Musculo-Skeletal Disorders - Osteoporosis By Kyle J,Norton

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.

I. Symptoms

1. Back pain, as a result of fractured or collapsed vertebra

In the study to investigate the prevalence and factors associated with low

back pain among adults in Taiwan. Methods: The National Health Interview

Survey, a cross-sectional study, was conducted from October 2002 to March

2003 to gather data from 24,435 adults aged 20 years and older selected

randomly from Taiwan's general population, showed that patients with

osteoporosis were more likely than those without osteoporosis to have low

back pain (OR = 2.55, 95% CI = 2.33-2.78) or frequent low back pain (OR =4.15, 95% CI = 3.66-4.70). The ORs of frequent low back pain in association

with osteoporosis in men and women were 5.77 (95% CI = 4.66-7.15) and

3.49 (95% CI = 2.99-4.07), respectively(1).2. Loss of height over time

In a study of 231 men and women over the age of 65 underwent DXA scan

of their spine and hip (including bone mineral density and Vertebral Fracture

Assessment), measurement of their height, and a questionnaire, showed that

height loss was significantly associated with a vertebral fracture (p=0.0160).The magnitude of the association translates to a 19% increase in odds for 1/2

in. and 177% for 3 in. Although 45% had osteoporosis by either bone

mineral density or fracture criteria, 30% would have been misclassified if

bone mineral density criteria were used alone(2).

Others showed that Osteoporosis is a recognised co-morbidity in patients

with chronic obstructive pulmonary disease (COPD) and may cause

excessive height loss resulting in the 'normal' values and disease progression

being under-estimated(3).

3. A stooped posturePostural deformity might represent another risk factor for postural instability

and falls. In the study to investigate the influence of spinal curvature on

postural instability in patients with osteoporosis, showed that no significant

correlations were observed between any parameters of postural balance and

angle of thoracic kyphosis. However, all parameters showed significant

positive correlations with angle of lumbar kyphosis (r = 0.251-0.334; p


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0.05-0.001). Moreover, lumbar kyphosis, but not thoracic kyphosis, showed

a positive correlation with spinal inclination (r = 0.692, p < 0.001), and all

parameters of postural balance showed significant positive correlations with

spinal inclination (r = 0.417-0.551, p < 0.001)(4).

4. Easy bone fracture

In a multicenter, double-blind, placebo-controlled trial of randomly assigned

1199 men with primary or hypogonadism-associated osteoporosis who were

50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5

mg) or placebo at baseline and at 12 months, found that Zoledronic acid

treatment was associated with a significantly reduced risk of vertebral

fracture among men with osteoporosis(5).

5. Neck and low back pain

In the study to determine the 1-year prevalence of neck pain and low backpain in the Spanish population and their association with sociodemographic

and lifestyle habits, self-reported health status and comorbidity with other

chronic disorders, found that neck and low back pain are prevalent and

highly associated between them, more frequent in female (particularly neck

pain) and associated to worse self-reported health status. Individuals with

neck and low back pain were more likely than those without pain to have

depression and other painful conditions, including headache and

osteoporosis(6)

6. Depression

Researchers showed there is negative associations between depression and

BMD variables in the three assessed areas. There were negative correlations

between anxiety, stress and spine BMD, as well as a tendency towards

negative relations in the right and left hip BMD. Concurrent hierarchical

regressions showed that the addition of the three psychological variables

increased the explained variance by 6-8 %. In addition, depression was

found to have a unique significant contribution to the explained variance in

right and left hip BMD(7).

7. Other symptoms

In the study to study compare symptoms at midlife, menopause attitudes,

and depression among three groups of late peri- or postmenopausal women,

namely, women with cardiovascular disease (CVD group), women with

osteoporosis (Os group), and women in generally good health (Co group),

showed that the CVD group reported significantly more severe symptoms at


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midlife than did the Co group; significantly more severe "psychosomatic

symptoms" than did the Co group; and significantly more severe

"gastrointestinal symptoms and swelling" and "vasomotor symptoms" than

did either the Os group or the Co group. The CVD group also reported

significantly greater depressive symptoms than did the Os group(8).

8. Etc.

II. Causes and Risk factors

A. Causes

1. SPRY1 gene

In the study to determine whether genetic variation in the human SPRY1

gene is associated with obesity-related phenotypes and/or osteoporosis in

humans, found that the four single nucleotide polymorphisms (SNPs) were

significantly associated with either obesity-related traits or osteoporosis. TheTGCC haplotype in the SRPY1 gene showed simultaneous association with

an increased risk for obesity-related traits, percentage body fat (p=0.0087)

and percentage abdominal fat (p=0.047), and osteoporosis (odds ratio=1.50;

p=0.025) in the recessive genetic model(9).

2. Other causes

According to the study by Dr. Fitzpatrick LA at the Division of

Endocrinology, Diabetes, Metabolism, Nutrition, and Internal Medicine,

Rochester, in some studies, 20% to 30% of postmenopausal women and

more than 50% of men with osteoporosis have a secondary cause. There are

numerous causes of secondary bone loss, including adverse effects of drug

therapy, endocrine disorders, eating disorders, immobilization,

marrow-related disorders, disorders of the gastrointestinal or biliary

tract, renal disease, and cancer(10).

Other study suggested that Secondary osteoporosis occurs in almost two-

thirds of men, more than half of premenopausal and perimenopausal women,

and about one-fifth of postmenopausal women. Its causes are vast, and they

include hypogonadism, medications, hyperthyroidism, vitamin D

deficiency, primary hyperparathyroidism, solid organ transplantation,gastrointestinal diseases, hematologic diseases, Cushing's syndrome,

and idiopathic hypercalciuria(11).

4. Etc.

B. Risk factors


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1. Young Age at Diagnosis, Male Sex, and Decreased Lean Mass

In the study to investigate the prevalence and identify the risk factors of

osteoporosis. METHODS:: Forty long-term survivors of osteosarcoma and

55 controls were enrolled. The mean age of the survivors was 21.85.2

years. They were diagnosed at younger than 23 years of age (mean, 14.9+5.0

y). Bone mineral densities (BMD) and body compositions were measured by

dual-energy x-ray absorptiometry, showed that nineteen (47.5%) subjects

had osteoporosis and 12 (30.0%) had osteopenia. The regions affected by

osteoporosis were: femur neck of osteosarcoma site (47.5%), unaffected

femur neck (12.5%), lumbar spine (12.5%), and total body (15.0%). Twelve

subjects (30.0%) had 14 episodes of fractures. The identified risk factors of

osteoporosis were young age at diagnosis, male sex, and low lean mass.

Subjects diagnosed before attainment of puberty (male16 y, female14 y)

were found to have a higher prevalence of osteoporosis (37.5% vs. 10.0%,

P


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how lactose maldigestion influences the risk for osteoporosis. Low calcium

intakes, a greater than previously thought potential for low bone density and

extensive lactose maldigestion among Hispanic-American and Asian-

American populations may create an elevated risk for osteoporosis(16).

6. Family history

In the study toassess the relationship between the prevalence of reported

physician-diagnosed osteoporosis and family history in a representative

sample of U.S. women, examine whether osteoporosis risk factors account

for this relationship, and evaluate the likelihood that women at high risk of

osteoporosis due to family history report preventive behaviors, showed that

family history is a significant, independent risk factor for osteoporosis in

U.S. women aged>or=35 years. Further studies are warranted to evaluate

family history as a convenient and inexpensive tool for identifying women at

risk of osteoporosis and for promoting the adoption of preventivebehaviors(17).

7. Skin color and body size

In the comparison of skin color, body size and bone mineral density (BMD)

among three groups of postmenopausal women: 104 healthy black women,

45 healthy white women, and 52 osteoporotic white women with vertebral

fractures. The osteoporotics are above the ideal body mass index

recommended by the National Institutes of Health, researchers found that

fair skin is not a risk factor for osteoporosis and that large body size is not

protective against the development of osteoporosis, although it may have a

salutary effect on BMD in both blacks and whites(18).

8. Diet and lifestyle

In the study of total of 632 women age > or =60 years were enrolled in this

study. Subjects were interviewed about their lifestyle by means of a

questionnaire regarding the consumption pattern ofdietary items, showed

that the BMD was higher in subjects with the habits of alcohol drinking,

green tea drinking, and physical activity and lower in those with the habits

of smoking and cheese consumption. Multiple regression analysis showedthat factors associated with BMD were smoking, alcohol consumption,

green tea drinking, and physical activity after adjusting for age and body

mass index (BMI)(19).

9. Heavy alcohol intake or alcoholism

Heavy alcohol intake or alcoholism, however, frequently disrupts calcium


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and bone homeostasis, which leads to reduce bone mineral density and

increase the incidence of fragility fracture, according to the studyby

Department of Endocrinology and Metabolism, Saitama Medical

School(20).

10. Smokingand lower serum IGF-I levels

In the study of age, body mass index, current smoking history, and serum

insulin-like growth factor-I levels associated with bone mineral density in

middle-aged Korean men, suggest that higher age, a lower BMI, current

smoking history, and lower serum IGF-I levels are risk factors for lower

BMD in middle-aged Korean men; however, serum testosterone levels and

GH secretory capacity were not found to be correlated with BMD(21).

11. Other risk factors

The frequency ofdecreased bone mineral density, vitamin and calciumdiet content and sufficiency with vitamins evaluated by means of blood

serum level determination among patients suffering from chronic diseases

(of cardiovascular system, gastrointestinal tract, osteopenia and

osteoporosis)(22).

III. Diagnosis

According to the Clinical practice guidelines for the diagnosis and

management of osteoporosis. Scientific Advisory Board, Osteoporosis

Society of Canada, Screening and diagnostic methods: risk-factor

assessment, clinical evaluation, measurement of bone mineral density,

laboratory investigations.

If you are experience certain symptom of osteoporosis, the tests which your

doctor order include

1. Blood and urinary tests

The aim of the tests are to check for the bone metabolismand the

progression of bone (loss) diseases.

2. Dual energy X-ray absorptiometry (DXA)Dual energy X-ray absorptiometry (DXA) is one most common test to

measure the total bone density of including spine, hip, wrist etc. with

accurate result.

3. Quantitative Ultrasound and computed tomography (QCT)

The evaluation of bone density at the lumbar spine and hip.using a standard


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that TFDG and EGCG inhibited the formation and differentiation of

osteoclasts via inhibition of MMPs. TFDG may suppress actin ring

formation more effectively than EGCG. Thus, TFDG and EGCG may be

suitable agents or lead compounds for the treatment of bone resorption

diseases(27).

2. Soy

In the study to clarify the effect of ingesting soy isoflavone extracts (not soy

protein or foods containing isoflavones) on bone mineral density (BMD) in

menopausal women, found that the varying effects of isoflavones on spine

BMD across trials might be associated with study characteristics of

intervention duration (6 vs. 12 months), region of participant (Asian vs.

Western), and basal BMD (normal bone mass vs. osteopenia or

osteoporosis). No significant effects on femoral neck, hip total, and

trochanter BMD were found. Soy isoflavone extract supplements increasedlumbar spine BMD in menopausal women(28).

3. Orange juice

In the study to evaluate the possible variations in antioxidant enzymes, lipid

peroxidation and erythrocyte deformability in experimentally induced

osteoporosis in female rats and to assess the effects of vitamin C

supplementation on those variations, indicated that BMD was significantly

lower in the group O than in the group C (p = 0.015), whereas it was

significantly higher in the group OVC than in the group O (p = 0.003). MDA

activity was significantly higher in the group O than in the group C (p =

0.032), whereas it was significantly lower in the group OVC than in the

group O (p = 0.025). SOD activity was significantly higher in the group O

than in the group C (p = 0.032). Erythrocyte deformability was significantly

higher in the group O than in the group C and OVC (p = 0.008, p = 0.021,

respectively)(29).

4. Milk thistle seeds

In the study to investigate that silibinin had bone-forming and

osteoprotective effects in in vitro cell systems of murine osteoblasticMC3T3-E1 cells and RAW 264.7 murine macrophages, found that that

silibinin retarded tartrate-resistant acid phosphatase and cathepsin K

induction and matrix metalloproteinase-9 activity elevated by RANKL

through disturbing TRAF6-c-Src signaling pathways. These results

demonstrate that silibinin was a potential therapeutic agent promoting bone-

forming osteoblastogenesis and encumbering osteoclastic bone


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resorption(30).

5. Skin and seed of grape

In the study to investigate the molecular mechanism of how resveratrol can

modulate the lineage commitment of human mesenchymal stem cells to

osteogenesis other than adipogenesis, showed that

resveratrol promoted spontaneous osteogenesis but prevented adipogenesis

in human embryonic stem cell-derived mesenchymal progenitors.

Resveratrol upregulated the expression of osteo-lineage genes RUNX2 and

osteocalcin while suppressing adipo-lineage genes PPAR2 and LEPTIN in

adipogenic medium. Furthermore, the osteogenic effect of resveratrol was

mediated mainly through SIRT1/FOXO3A with a smaller contribution from

the estrogenic pathway(31).

6. Etc.

B. Antioxidant vitamins and minerals to prevent Osteoporosis

1. In the study to evaluate whether antioxidant defenses are decreased in

elderly osteoporotic women and, if this is the case, to understand whether

osteoporosis is a condition characterized by increased oxidative stress,

researchers at the Gerontology and Geriatrics, University of Perugia, found

that dietary and endogenous antioxidants were consistently lower in

osteoporotic than in control subjects. On the other hand, plasma levels of

malondialdehyde, a byproduct of lipid peroxidation, did not differ between

groups. Our results reveal that antioxidant defenses are markedly decreased

in osteoporotic women. The mechanisms underlying antioxidant depletion

and its relevance to the pathogenesis of osteoporosis deserve further

investigation(32).

2. Selenium plus vitamins E and C

In the study to to investigate the effect of heparin on osteoporosis initiation,

and the effect of selenium plus vitamins E and C, and the sole combination

of vitamins E and C on the progress of osteoporosis induced by heparin

through histologic means, showed that the combination of vitamins E and Cgiven to the experimental rabbits partially prevented this bone tissue

destruction. When sodium selenite was given together with vitamins E and C

to the osteoporosis model rabbits, the long bone tissue had almost the same

structure as in normal rabbits, for example the development of numerous

bone trabeculae(33).


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3. Vitamin C

According to the study epidemiologic studies correlate low vitamin C intake

with bone loss. The genetic deletion of enzymes involved in de novo vitamin

C synthesis in mice, likewise, causes severe osteoporosis. In the study of

Vitamin C prevents hypogonadal bone loss by School of Stomatology,

Wuhan University, Wuhan indicated that the ingestion of vitamin C prevents

the low-turnover bone loss following ovariectomy in mice. This prevention

in areal bone mineral density and micro-CT parameters results from the

stimulation of bone formation, demonstrable in vivo by histomorphometry,

bone marker measurements, and quantitative PCR. Notably, the reductions

in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast

gene expression 8 weeks post-ovariectomy are all returned to levels of sham-

operated controls(34).

4. Calcium and vitamin D

Calcium supplements reduce the rate of bone loss in osteoporotic patients.

Some recent studies have reported a significant positive effect of calcium

treatment not only on bone mass but also on fracture incidence. The

SENECA study, has also shown that vitamin D insufficiency is frequent in

elderly populations in Europe. There are a number of studies on the effects

of vitamin D supplementation on bone loss in the elderly, showing that

supplementations with daily doses of 400-800 IU of vitamin D, given alone

or in combination with calcium, are able to reverse vitamin D insufficiency,

to prevent bone loss and to improve bone density in the elderly, according to

the Dr. Gennari C. by Institute of Internal Medicine, University of Siena(35)

5. Etc.

V. Treatments

A. In conventional medicine perspective

A.1. Bisphosphonates

1. Including Alendronate (Fosamax), Risedronate (Actonel, Atelvia),

Ibandronate (Boniva), Zoledronic acid (Reclast, Zometa), etc..Bisphosphonates are antiresorptive medications widely prescribed for

treating osteoporosis. In placebo-controlled clinical trials they have been

shown to significantly reduce the risk of osteoporotic fractures(36).

Others suggested that Because bisphosphonate accumulate in bone and

provide some residual antifracture reduction when treatment is stopped, we

recommend a drug holiday after 5-10 yr of bisphosphonate treatment. The


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duration of treatment and length of the holiday are based on fracture risk and

pharmacokinetics of the bisphosphonate used. Patients at mild risk might

stop treatment after 5 yr and remain off as long as bone mineral density is

stable and no fractures occur. Higher risk patients should be treated for 10

yr, have a holiday of no more than a year or two, and perhaps be on a

nonbisphosphonate treatment during that time(37).

2. Side effects

a. Nausea

b. Abdominal pain

c. Difficulty swallowing

d. Rrisk of an inflamed esophagus or esophageal ulcers(38)

e. Risk of scleritis and a variety of ocular side effects(39)

f. Etc.

2. Hormone-related therapy

Hormone replacement therapy can help to maintain bone density for

menopause women, but it increases

a, The risk of breast cancer and heart disease(40)

b. The risk for venous thromboembolism(41)

c. The risk of (Nonmelanoma Skin Cancers) NMSC.(42)

d. The risk of stroke(43)

e. etc.

B. In herbal medicine perspective

1. Red clover

In the study to test the combined effect of a quality-controlled red clover

extract (RCE) standardized to contain 40% isoflavones by weight (genistein,

daidzein, biochanin A, and formononetin present as hydrolyzed aglycones)

together with a modified alkaline supplementation on bone metabolic and

biomechanical parameters in an experimental model of surgically-induced

menopause, showed that red clover preparation in dosages amenable to

clinical practice do improve OVX-induced osteoporosis while a mild

metabolic alkalosis might further synergize some therapeutic aspects(44).

2. Soy

In the study to to examine whether soybean protein isolate prevents bone

loss induced by ovarian hormone deficiency, researchers at the Department

of Human Nutrition and Dietetics, University of Illinois at Chicago,

indicated that despite the higher rate of bone turnover in the soybean-fed


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(BL 23) for preventing and treating primary osteoporosis, found that BMDs

of hip and lumbar vertebrae were both increased in the embedding thread

group, and the BMDs of femoral neck and femoral trochanter in this group

were significantly higher than those in the medication group (both P < 0.05).

The rate of bone fracture during 5 years after treatment was 2.1% (1/48) in

the embedding thread group, which was significantly lower than 18.2%

(4/22) in the medication group (P < 0 05)(49).

4. Shaoyang Meridians

In the review to explore the theory of "Shaoyang Meridians being in charge

of the bone" in Huangdi's Internal Classic, which has been buried for long

time, indicated that the theory of "Shaoyang Meridians being in charge of

the bone" possibly first in the world recognizes osteoporosis being a general

bony disease, and articulates that the Foot-Shaoyang Meradians can

modulate bony strength under physiological and pathological conditions,and treat osteoporosis which mainly manifests as ostealgia and easy

fracture(50).

5. Kidney-replenishing herbs (KRH)

In the study to investigate the effect of Kidney-replenishing herbs (KRH) on

ovarian function of experimental rats with dexamethasone-induced

osteoporosis (OP), showed that KRH could elevate the level of GH, LH,

FSH, E2 and P, increase the weight and improve the histomorphologic

features of ovary and uterus in OP rats(51).

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Musculo-Skeletal Disorders - Osteoporosis