Osteoporosis

Definition/Description[edit | edit source]

Osteoporosis is a disease characterized by a decrease in bone density (mass and quality). It is a disorder in which bones become increasingly porous and brittle leading to increased risk of fracture. Osteoporosis is a major health threat across the globe.[1] Osteoporosis means porous bone, normal healthy bone looks like a honeycomb in microscopic view, in osteoporosis due to the loss in bone mass and bone protein it looks porous. In the United States alone, approximately 10 million individuals are estimated to already have the disease and 34 million at increased risk for osteoporosis.[2] Fifty-five percent of Americans over the age of 50 have the disorder. [2]

There are two types of osteoporosis: primary and secondary.[3]

Primary osteoporosis is unrelated to other diseases or conditions and is the more common of the two. It is most common in postmenopausal women or older men, but can occur at any age. In cases of primary osteoporosis, either the condition is caused by age-related bone loss (sometimes called senile osteoporosis) or the cause is unknown (idiopathic osteoporosis).[3]

In cases of secondary osteoporosis, the loss of bone mass is caused by certain lifestyle behaviors, diseases, or medications.[3] The most common causes of secondary osteoporosis in men include exposure to glucocorticoid medications, hypogonadism  (low levels of testosterone), alcohol abuse, smoking, gastrointestinal disease, hypercalciuria, and immobilization.[3]

Diagnosis[edit | edit source]

Bone frailty leads to an increased risk for fractures. Osteopenia is a term that has been used to describe a decrease in bone mass. Experts prefer the term low bone mass. T-scores were often used to classify individuals as osteoporotic. Early in the diagnosis of osteoporosis, the World Health Organization, defined a normal bone mineral density score is -1.0 or higher, -1.0 to -2.5 for osteopenia, and -2.5 or lower for osteoporosis.[4] Today, the Fracture Risk Assessment Tool, FRAX,  has become a more accurate way to measure 10years fracture probability.  The FRAX questionnaire takes into account elements that influence an individual's bone quality as well as their bone density. [5]

To learn more about FRAX view this tutorial.



Prevalence[edit | edit source]

Osteoporosis is the most prevalent bone disease in the world. [2]According to the National Osteoporosis Foundation, about 10 million Americans currently have osteoporosis, while about 34 million are at risk for the disease.[2]In cases of primary osteoporosis, either the condition is caused by age-related bone loss (sometimes called senile osteoporosis) or the cause is unknown (idiopathic osteoporosis).[3] It is estimated that one in two women over the age of 50 and one in four men will break a bone because of osteoporosis.[2] It is projected that by 2020, half of Americans over the age of 50 will have osteoporosis or low bone density.[6]

Characteristics/Clinical Presentation[edit | edit source]

Osteoporosis is often referred to as a silent disease because there are no early clinical signs or symptoms. Frequently, no symptoms are present until bone loss is advanced enough to result in a fracture. Common locations of fracture include: proximal femur, vertebrae, hip, pelvis, proximal humerus, distal radius, and tibia. Proximal femur and vertebrae are the two most common sites. Therefore, constant mild to severe back pain may be a concern when there is no history of injury or falls. Hip fractures are usually not detected until a fall has occurred. Because of the lack of early symptoms, those at risk are highly suggested to get routine bone scans. Many individuals will develop secondary orthopedic problems related to postural changes, fractures, and a general decrease in physical conditioning that often accompanies the disease.[5] A common presentation of an individual with osteoporosis may be a Caucasian female, 65 years or older, with a thin body type.

==Clinical Signs and Symptoms [7][edit | edit source]

  • Back pain: Episodic, acute low thoracic/high lumbar pain
  • Compression fracture of the spine 
  • Bone fractures
  • Decrease in height 
  • Kyphosis
  • Dowager’s hump
  • Decreased activity tolerance
  • Early satiety

Associated Co-morbidities[edit | edit source]

As many diseases increase an individual's risk of osteoporosis, they also may be seen as comorbidities.[7]

  • Eating disorders
  • Cancer and cancer treatment
  • Chronic renal failure
  • Osteogenesis imperfect
  • Rheumatic diseases
  • Chronic pulmonary disease
  • Cushing’s Disease
  • Male hypogonadism
  • Hypothyroidism
  • Hyperparathyroidism
  • Type 2 Diabetes Mellitus
  • Gastrointestinal Disease
  • Hepatic disease

The following comorbidities should may increase the risk of fracture:[7]

  • Inflammatory bowel or joint disease
  • Breast or prostate cancer
  • Diabetes
  • Celiac diseases
  • Moderate Renal Failure
  • Depression                                                                                                                                                  



Medications[edit | edit source]

Class and Drug Brand Name Form Frequency Side Effects
Biphosphonates
Alendronate Generic Alendronate and Fosamax Oral (tablet) Daily/Weekly

Side effects for all biphosphonates may include bone, joint, or muscle pain.

Side effects of the oral tablets may include nausea, difficulty swallowing, heartburn, irritation of the esophagus, and gastric ulcer.

Side effects that can occur shortly after receiving an IV biphosphonate include flu-like symptoms, fever, headache, and pain in muscles or joints.

Alendronate Fosamax Plus D (with 2,800 IU or 5,600 IU of Vitamin D3) Oral (tablet) Weekly
Ibandronate Boniva Oral (tablet) Monthly
Ibandronate Boniva Intravenous (IV) injection Four times per year
Risedronate Actonel Oral (tablet) Daily/Weekly/Twice Monthly/Monthly
Risedronate Actonel with Calcium Oral (tablet) Weekly
Zoledronic Acid Reclast Intravenous (IV) infusion One time per year/Once every two years
Calcitonin
Calcitonin Fortical Nasal spray Daily Runny nose, headache, back pain, and nosebleed (epistaxis)
Calcitonin Miacalcin Nasal spray Daily
Calcitonin Miacalcin Injection Varies May cause an allergic reaction and unpleasant side effects including flushing of the face and hands, urinary frequency, nausea, and a skin rash.
Estrogen
Estrogen Multiple brands Oral (tablet) Daily Increased risk of endometrial and breast cancer, vaginal bleeding, breast tenderness, gallbladder disease, stroke, venous blood clot, cognitive decline.
Estrogen Multiple brands Transdermal (skin patch) Twice Weekly/Weekly
Estrogen Agonists/Antagonists also called Selective Estrogen Receptor Modulators (SERMs)
Raloxifene Evista Oral (tablet) Daily Hot flashes, leg cramps, and deep vein thrombosis (blood clots)
Parathyroid Hormone
Teriparatide Forteo Injection Daily Leg cramps and dizziness
RANK Ligand (RANKL) Inhibitor
Denosumab Prolia Injection Every 6 Months May lower calcium levels in the blood. May also increase the risk of injection and skin rashes.

[8]  

Antiresorptive medications, such as biphosphonates, calcitonin, denosumab, estrogen, and estrogen agonists/antagonists, work to prevent more bone loss and reduce the risk of fractures.[9]

Anabolic drugs, such as Teriparatide (a parathyroid hormone), work to increase the rate of bone formation and reduce the risk of fractures.[9]

Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]

In order to make a diagnosis of osteoporosis there are series of diagnostic tests and lab tests that your doctor may perform after taking a thorough patient history and performing an examination.

Bone Density Test[edit | edit source]

The most common test used is a bone density test, which is the only test that can detect osteoporosis before a fracture occurs. There are two types of bone density tests: Central DXA and Screening Tests. Central DXA uses a dual energy absorptiometry machine to test the bone density of the hip and spine. If testing can’t be done to the hip and spine then it is recommended to test the radius of the forearm. Central DXA is the preferred method because it measures bone density at the hip and spine where bone loss occurs most rapidly.[10]

Screening Tests, also called peripheral tests, measure bone density in the lower arm, wrist, finger, or heel. These are useful when Central DXA testing is not possible. Screening tests cannot accurately diagnose osteoporosis or measure how well medication is working.[10]

Bone density test results are reported using T-scores. T-scores are relative to how much higher or lower your bone density is compared to that of a healthy 30 year old adult.[10]

Category
T-score
Normal
-1.0 or above
Osteopenia (low bone mass)
-1.0 to -2.5
Osteoporosis
-2.5 or less
Severe Osteoporosis
-2.5 or less with one or more fragility fractures

Laboratory Tests[edit | edit source]

  • Blood Calcium levels
  • 24-hour urine calcium measurement
  • Thyroid function tests
  • Parathyroid hormone levels
  • Testosterone levels in men
  • 25-hydroxyvitamin D test to determine whether the body has enough vitamin D
  • Biochemical marker tests, such as NTX and CTX

Some of these tests can help to identify if you have any other medical conditions that could contribute to osteoporosis, which would be called secondary osteoporosis. Biochemical marker tests can help estimate how fast you are losing or making bone.[11]

Etiology/Causes[edit | edit source]

Bone tissue is constantly being absorbed and replaced throughout ones life span. Bone mass decreases when the rate of absorption increases the rate or production; typically occurring with advanced age. Peak bone mass is met at the average age of 20. Those who develop less bone mass prior to this time, have a high chance of developing osteoporosis.[12]

Primary osteoporosis has no known definite cause, but there are many contributing factors associated with the disorder. These include prolonged negative calcium balance, impaired gonadal and adrenal function, estrogen deficiency, or sedentary lifestyle. Postmenopausal osteoporosis is associated with increased bone loss due to decrease production of estrogen.[5] Women commonly lose 1% per year after peak bone density has been met, for up to 8 years post menopause.[13] Senile osteoporosis is an age-related bone loss that often accompanies advanced aging.[5]

Secondary osteoporosis is caused by prolonged use of medications or secondary to another disease or condition which inhibits the absorption of calcium or impedes the body's ability to produce bone.[5]

Low calcium intake or absorption can greatly increase one's risk for developing osteoporosis. Life long calcium intake is crucial in building up bone stock prior to peak levels of bone mass, as well as maintain bone mass after the age of 20. Excessive alcohol consumption can decrease the body's ability to absorb calcium.[14]

Bone produces in response to the load applied to it. Physically active individuals typically have higher bone density, than those who have a sedentary lifestyle.[14]

Hormone levels, either too little or too much, can impede on the body's ability to produce and maintain adequate bone mass. Dysfunction with sex glands, thyroid, parathyroid, or adrenal glands is often associated with osteoporosis. [14]

Risk Factors[5][edit | edit source]

  • Age 50 years and older
  • Female gender
  • Caucasian and Asian
  • Menopause (especially early or surgically induced)
  • Family history of osteoporosis or fragility fractures
  • Northern European ancestry
  • Long periods of inactivity or immobilization
  • Depression
  • Alcohol (>3 drinks/day)
  • Tobacco
  • Caffeine (>4 cups/ day)
  • Amenorrhea (abnormal absence of menses)
  • Thin body build

Other risk factors - Long term use of long-acting benzodiazepines, anticonvulsants or corticosteroids, low testosterone levels in men and anorexia or poor dietary intake

Associated Diseases & Disorders: [5][edit | edit source]

Endocrine Disorders:

  • Hypothyroidism
  • Hyperparathyroidism
  • Type 2 Diabetes Mellitus
  • Cushing’s Disease
  • Male hypogonadism (testosterone deficiency) Malabsorption syndrome:
  • Gastrointestinal disease; gastric surgery
  • Hepatic disease

Medication-related:

Organ transplant

  • Chronic pulmonary disease
  • Rheumatic diseases, including juvenile rheumatoid arthritis

Other:

  • Chronic renal failure
  • Osteogenesis imperfect
  • Cancer and cancer treatment; skeletal metastases
  • Eating disorders
  • Spinal cord injury
  • Cerebrovascular accident or stroke
  • Acid-balance imbalance (metabolic acidosis)
  • Depression (men > women)

Medication (>6 months)[5][edit | edit source]

  • Corticosteroids/steroids
  • Immunosuppressants
  • Heparin; Coumadin (Wafarin)
  • Nonthiazide diuretics
  • Methotrexate
  • Chemotherapy
  • Antacids (containing aluminum)
  • Laxatives
  • Anticonvulsants
  • Some antibiotics
  • Buffered aspirin
  • Thyroid hormone
  • Lithium
  • Depo-provera (contraceptive)

Diet & Nutrition[5][edit | edit source]

  • Calcium and magnesium deficiency
  • Vitamin D deficiency
  • Vitamin C deficiency (helps with calcium absorption)
  • High ratio of animal to vegetable protein intake
  • High-fat diet (reduces calcium absorption in the gut)
  • Excess sugar (depletes phosphorus)
  • Eating disorders or repeated crash dieting

Systemic Involvement[edit | edit source]

An excess of calcium due to the addition of supplements to one's diet can lead to urinary dysfunction, mild diarrhea, or constipation and should be discussed with your doctor if it does not resolve.[5]

In a study performed by Leech JA, Dulberg C, Kellie S, Pattee L, Gay J, the relationship of lung function compared to severity of osteoporosis in women was studied. Results showed that kyphosis and thoracic compression fractures due to osteoporosis can produce modest declines in vital capacity.[15]

Medical Management (current best evidence)[edit | edit source]

According to Kurt Kennel, M.D., an endocrinology specialist from the Mayo Clinic, the most common medications used to manage osteoporosis are biphosphonates, such as Fosamax, Boniva, Actonel, Atelvia, Reclast, and Zometa. It is also a common practice to use hormones, like estrogen, to help treat and prevent osteoporosis. Some women do not elect to use these hormones due to the increased risk of heart attacks and certain types of cancers. The choice of which drug is right for you is generally based on preference, convenience, and adhering to dosing schedule.[16]

The length of time that a medicine should be used is variable. Most current research shows that biphosphonate medications should be taken up to 5 years for it to be safe and effective. There haven't been enough long-term studies to prove the efficiency of the medications after 5 years of treatment. One thing is known that if you have been taking biphosphonate drugs you can still have positive effects after you stop taking the medications due to building up the medicine in your bone. Due to this effect of the medications, some doctors have patients take a break from the medications after 5 years if they believe they are at a low-risk for fractures.[16]

Medical management helps reduce the risk of fractures but does not eliminate it. If you experience a fracture while taking medications to help treat your osteoporosis you may need to switch to a more aggressive bone-building therapy, such as Forteo (a parathyroid hormone), or a new osteoporosis drug like Prolia or Xgeva. These drugs produce similar or better results than biphosphonates but just work in a different way.[16]

Medical management isn't the only way to treat osteoporosis. It is also important to include daily exercise, good nutrition (including the adequate amount of calcium and vitamin D), quit smoking, and limit your alcohol intake.[16]

Physical Therapy Management (current best evidence)[edit | edit source]

Physical therapy intervention for individuals with osteoporosis, or even osteopenia, should include:

  • weight-bearing
  • flexibility exercise
  • strengthening exercise
  • postural exercise
  • balance exercise

Weight-bearing exercises[edit | edit source]

Exercises such as walking or hopping, has been shown to maintain or improve bone density in this population. Strengthening exercises, using weights or resistance bands, has also be shown to maintain or improve bone density at the location of the targeted muscle attachments. Maintaining bone health in this population is extremely important, especially in the elderly as there is typically has a decline in bone mass with age.[17] (level of evidence 2a)

Flexibility and strengthening exercises[edit | edit source]

These can help improve the individuals overall physical function and postural control. Improving postural control is important to reduce the risk for falls. Falls often result in fractures in frail individuals. Balance exercises are also important to incorporate to further reduce the risk of falls.[18] (level of evidence 1b)

Postural exercises[edit | edit source]

These are crucial to prevent structural changes that often accompany osteoporosis, such as thoracic kyphosis. Every osteoporosis program should include extension exercises; chin tucks, scapular retractions, thoracic extensions, and hip extensions. Strengthening the extensor muscles will promote improved posture and improved balance. Flexion exercises are CONTRAINDICATED. Anterior compressive forces to the vertebra can contribute to compression fractures.[5] (level of evidence 5)

Back pain[edit | edit source]

Physical therapist may treat patients with osteoporosis for back pain. Agility training, resistance training, and stretching have all been shown to decrease back pain and its related disabilities in this population.[19] (level of evidence 1b)

High intensity training[edit | edit source]

Research highly supports high intensity training in the prevention of bone lost for women in menopausal years and early stage post menopausal. High intensity training would include body-weight and resistive exercises at a high intensity, similar to circuit training.[20] (level of evidence 1a) Most of these studies have been performed on individuals who have NOT been diagnosed with osteoporosis. This type of training is often contraindicated for individuals with low bone mass.

A Cochrane review has been completed to determine the best exercise for prevention and treatment of osteoporosis. The population was healthy post menopausal females, age 45- 70. Duration of the intervention was at the least ten months, several lasting over a year. The majority of the studies has a frequency of 2- 3 days per week. The results were that combination of exercise promotes greatest improvements in bone mass at the spine, wards triangle, and the femoral trochanter. Dynamic weight-bearing, high force exercise results with greatest improvements at the femoral neck and moderate results at the femoral trochanter. Dynamic weight-bearing, low force exercise had moderate positive effects at the spine. Non-weight-bearing, high force exercise were shown to have moderate effects at the femoral neck.[21] (level of evidence 1a)

Clinical Considerations[edit | edit source]

Metabolic bone diseases results in impaired healing rates, therefore should be considered when determining prognosis.[5] (level of evidence 5)

Manipulations: A strong precaution should be taken before performing manual techniques such as manipulations or joint assessments that may increase an individuals risk for fractures, especially in the spine. Further studies need to be conducted to determine clinical guidelines for manipulation in osteoporotic individuals.[22] (level of evidence 4c)

Body Weight Supported Treadmill Training: It is contraindicated to use body weight supported treadmill training with individuals who have severe osteoporosis or lower extremity, pelvic, or rib fracture. Severe osteoporosis is considered a T-score greater than 2.5.[23] (level of evidence 1a) (guideline withdrawn)

Practice Patterns:[5] (level of evidence 5)

  • 4A: Primary Prevention/ Risk Reduction for Skeletal Demineralization
  • 4B: Impaired Posture
  • 4C: Impaired Muscle Performance
  • 4F: Impaired Joint Mobility, Motor Function, Muscle Performance, Range of Motion, and Reflex Integrity Associated with Spinal Disorder
  • 4G: Impaired Joint Mobility, Muscle Performance, and Range of Motion Associated with Fracture

Dietary Management [edit | edit source]

Diet has a direct correlation to bone growth and as we age we may not be absorbing the adequate amount of calcium. By including a variety of calcium-rich foods, such as milk, cheese, almonds, broccoli, and cauliflower you can make sure that you are getting the amount of calcium that you need.[24] It is also recommended that a person with osteoporosis should not have a high-protein diet. When the kidneys flush out excess protein they also flush out calcium. Caffeine is also known to inhibit calcium absorption so you should limit your caffeine intake to the equivalent of 3 cups of coffee a day. While most leafy green vegetables are a great addition to the diet of someone with osteoporosis it has been shown that oxalate acid that is found in spinach prevents absorption of calcium in the stomach. Kale and other geen vegetables that contain calcium would be better choices.[25]

Vitamin supplements may also be necessary when managing osteoporosis. According to the University of Maryland Medical Center (UMMC), 1,500 milligrams of calcium, taken in 3 doses of 500 milligrams per day, is an effective supplement to strengthen the bones and prevent further bone loss. Other vitamins that are recommended to retain bone strength are vitamins D and K. But be careful not to exceed 1,000 milligrams of vitamin D or 500 micrograms of vitamin K daily. Another helpful addition would be to add 4 grams of fish oils to help increase the amount of calcium that your body absorbs and decrease the amount it loses.[25]


Differential Diagnosis[edit | edit source]

It is important to ensure the cause of low bone denisty has been properly diagnoised. The treatments will vary greatly.

  • Osteomalacia/ Rickets: Osteomalacia is softening of the bones due to a Vitamin D deficiency in adults, which can result in decalcification of the bone, fractures, skeletal deformities, bone pain and muscle weakness. Rickets is a similar condition in children.[5]
  • Paget's Disease: Bone is resorbed and formed at an increased rate, which may lead to pain, fractures, deformity, headaches, dizziness, osteoarthritis, spinal stenosis, and increased size of clavicle are a few common presentation.[5]
  • Bone Infection
  • Pediatric osteogenesis imperfecta
  • Cancer: Fractures caused by little or no force often occur due to osteoporosis, but may also be result of bone cancer or metastatic cancer.
  • Multiple Myeloma
  • Renal osteodystrophy
  • Scurvy: Vitamin C deficiency [26]

Case Reports/ Case Studies[edit | edit source]

The Effects of Whole Body Vibration on Bone Mineral Density for a Person with a Spinal Cord Injury: A Case Study

scholarworks.boisestate.edu/cgi/viewcontent.cgi

Asymmetric lower-limb bone loss after spinal cord injury: Case report

web.ebscohost.com/ehost/pdfviewer/pdfviewer

Resources[edit | edit source]

National Osteoporosis Foundation http://www.nof.org/

Journal of the American Physical Therapy Association www.physther.org/content/67/7/1100.full.pdf

Cochrane Review onlinelibrary.wiley.com/doi/10.1002/14651858.CD000333.pub2/abstract


References[edit | edit source]

  1. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17:1726-1733.
  2. 2.0 2.1 2.2 2.3 2.4 National Osteoporosis Foundation Report Finds Patient-Centered Care Is Key Element in Delivering High-Quality, High-Value Treatment. 2019. Available from: https://www.nof.org/news/national-osteoporosis-foundation-report-finds-patient-centered-care-is-key-element-in-delivering-high-quality-high-value-treatment/ (accessed 14 October 2019)
  3. 3.0 3.1 3.2 3.3 3.4 National Institutes of  Health Osteoporosis and  Related  Bone Diseases ~  National Resource Center chfs.ky.gov NIHOosteoporosisinmen
  4. Wright NC, Looker AC, Saag KG et al. (2014) The Recent Prevalence of Osteoporosis and Low Bone Mass in the United States Based on Bone Mineral Density at the Femoral Neck or Lumbar Spine. J Bone Miner Research. 29(11): 2520–2526. doi:10.1002/jbmr.2269.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 Goodman. Fuller. Boissonnault. Pathology; Implications for the Physical Therapist. 2nd. Philadelphia: Saunders, 2003. (level of evidence 5)
  6. National Osteoporosis Foundation. What is osteoporosis? http://www.nof.org/articles/7 (accessed 28 March 2013).
  7. 7.0 7.1 7.2 Goodman. Snyder. Differential Diagnosis for Physical Therapists; Screening for Referral. 4th. St.Louis: Saunders, 2007.
  8. National Osteoporosis Foundation. Treatment with Osteoporosis Medication. http://www.nof.org/articles/21 (Accessed 28 March 2013).
  9. 9.0 9.1 National Osteoporosis Foundation. Types of Osteoporosis Medications. http://www.nof.org/articles/22 (Accessed 28 March 2013).
  10. 10.0 10.1 10.2 National Osteoporosis Foundation. Having a Bone Density Test. http://www.nof.org/articles/743 (Accessed 28 March 2013).
  11. National Osteoporosis Foundation. Making a Diagnosis. http://www.nof.org/articles/8 (Accessed 28 March 2013).
  12. Mayo Clinic. Osteoporosis. http://www.mayoclinic.com/health/osteoporosis/DS00128 (accessed 28 March 2013)
  13. Mayo Clinic. Osteoporosis Causes. http://www.mayoclinic.com/health/osteoporosis/DS00128/DSECTION=causes (accessed 28 March 2013)
  14. 14.0 14.1 14.2 Mayo Clinic. Osteoporosis: Risk Factors. http://www.mayoclinic.com/health/osteoporosis/DS00128/DSECTION=risk%2Dfactors (accessed 28 March 2013)
  15. Leech JA, Dulberg C, Kellie S, Pattee L, Gay J. Relationship of lung function to severity of osteoporosis in women. Am Rev Respir Dis. 1990 Jan;141(1):68-71.http://www.ncbi.nlm.nih.gov/pubmed/2297189 (Accessed 28 March 2013).
  16. 16.0 16.1 16.2 16.3 Mayo Clinic. Osteoporosis treatment: Medication can help. http://www.mayoclinic.com/health/osteoporosis-treatment/WO00127 (Accessed 28 March 2013).
  17. Zehnacker CH, Bemis‐Dougherty A. Effect of Weighted Exercises on Bone Mineral Density in Post Menopausal Women A Systematic Review. Journal of Geriatric Physical Therapy. 2007; 30(2):79-88. (level of evidence 2a)
  18. Burke TN, Franca FJR, Ferreira de Meneses SR, Pereira RMR, Marques AP. Postural control in elderly women with osteoporosis: comparison of balance, strengthening and stretching exercises. A randomized controlled trial. Clinical Rehabilitation; 26 (11): 1021-1031. (level of evidence 1b)
  19. Liu-Ambrose TYL, Khan KM, Eng JJ, Lord SR, Lentle B, McKay HA. Both resistance and agility training reduce back pain and improve health-related quality of life in older women with low bone mass. Osteoporosis International; 16: 1321- 1329. (level of evidence 1b)
  20. Martyn-St James M, Carroll S. High Intensity resistance training and postmenopausal bone loss: a meta-analysis. Osteoporosis International; 17: 1225-1240. (level of evidence 2b)
  21. Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women (Review). The Cochrane Collaboration. 2011;(2). (level of evidence 1a)
  22. Sran MM, Khan KM. Physiotherapy and osteoporosis: practice behaviors and clinicians' perceptions--a survey. Manual Therapy. 2005 Feb;10(1):21-7. (level of evidence 4c)
  23. U.S. Department of Health & Human Services. National Guideline Clearing House. Best evidence statement (BESt). Intensive partial body weight supported treadmill training. http://guideline.gov/content.aspx?id=24531&search=Gait+training+procedure+ (accessed 28 March 2013) (level of evidence 1a)
  24. Livestrong. 3 Ways to Use Holistic Medicine to Treat Osteoporosis. http://www.livestrong.com/article/8328-use-holistic-medicine-treat-osteoporosis/ (accessed 28 March 2013).
  25. 25.0 25.1 Livestrong. Alternative Medicine & Diets for Osteoporosis. http://www.livestrong.com/article/22197-alternative-medicine-diets-osteoporosis/?utm_source=dontgo2&utm_medium=a3 (Accessed 28 March 2013).
  26. Medscape. Osteoporosis Differential Diagnoses. http://emedicine.medscape.com/article/330598-differential (accessed 28 March 2013)