Osteoporosis in Rehabilitation

DISEASE/DISORDER:

Definition

Osteoporosis translates to “porous bones” in Greek. The World Health Organization (WHO) defines osteoporosis as a bone mineral density (BMD) at the femoral neck, total hip or lumbar spine that is 2.5 standard deviations or more below the young female adult mean, known as the T-score.¹  Osteoporosis is the most common metabolic bone disease, causing more than 8.9 million fractures annually worldwide.

Etiology

Osteoporosis is a disorder characterized by low bone mass and microarchitectural changes in bone tissue that lead to increased bone fragility and fracture risk.² It results from changes in the bone remodeling process, which occurs during the skeletal life cycle. Osteoporosis can be either primary or secondary in etiology. Primary osteoporosis is more common than secondary osteoporosis and can be divided into postmenopausal osteoporosis (Type 1, occurring in women aged 50-65 years with a phase of accelerated bone loss) and age-associated or senile osteoporosis (Type 2, occurring in women and men older than 70 years with bone loss associated with age). Secondary osteoporosis is a result of medical conditions or treatments that alter bone remodeling.³

Epidemiology including risk factors and primary prevention

An estimated 200 million people have osteoporosis worldwide, and an estimated 54 million Americans have either osteoporosis or low bone density.⁴ The hip, spine and wrist are most likely to be affected, with hip fractures accounting for 14% of incident fractures and 72% of fracture costs. The cost of care is expected to rise to $25.3 billion by 2025.³ It is often diagnosed by the occurrence of a fragility fracture.  There are multiple risk factors associated with the development of osteoporosis; these include (but are not limited to) increasing age, female sex, race (Caucasians and Asians are higher risk), low body mass index, hypogonadism or premature ovarian failure, previous history of fractures from low-intensity or minimal trauma and pre-existing medical conditions, such as Cushing’s syndrome, diabetes mellitus, multiple myeloma, and stroke. Social risk factors include cigarette smoking, alcohol abuse, and lack of exercise. Diets low in calcium or vitamin D, excess vitamin A, high salt intake, low estrogen levels in women, and low testosterone levels in men all increase the likelihood of developing osteoporosis and osteoporosis-related fractures.  Lastly, a number of medications have been shown to negatively impact bone density, including corticosteroids, anticonvulsants, antacids, and heparin.

Patho-anatomy/physiology

Peak bone mass is achieved by age 18-25. As we age, daily bone remodeling occurs. Effective remodeling depends upon a balance between bone resorption and bone deposition. The bone remodeling cycle is such that osteoclasts are activated, resulting in bone resorption. Next, osteoblasts lay down new bone matrix. Osteoblastic activity requires more time than osteoclastic activity, and thus, there is a tendency for overall bone loss when there is an increase in bone resorption. Eventually, this can lead to disordered skeletal architecture and an increase in fracture risk.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

The WHO describes 4 stages of progressively worsening BMD: normal bone mass, low bone mass (osteopenia), osteoporosis, and severe/established osteoporosis.  These stages are based on BMD scores, as determined by central dual-energy x-ray absorptiometry (DXA), and their corresponding T-scores and Z-scores.⁵

Normal bone mass is defined as a BMD within 1 standard deviation of the mean BMD in a young-adult reference population (T-score ≥ -1).  Low bone mass (osteopenia) is defined as a BMD between 1 and 2.5 standard deviations below the mean BMD (T-score between -1 and -2.5).  Osteoporosis is defined as a BMD more than 2.5 standard deviations below the mean (T-score ≤ -2.5). Severe/established osteoporosis is defined as osteoporosis in the setting of at least 1 fracture.⁵  It is important to note that T-scores should only be used for postmenopausal women and men over 50 years of age. A Z-score compares the BMD of the individual to the mean of those in their own age and gender group and should be used for children, premenopausal women and men under 50 years of age. A Z-score >2 SD below the mean may warrant further work-up to investigate secondary causes of bone fragility.⁴

Specific secondary or associated conditions and complications

The conditions most commonly associated with osteoporosis are vertebral body, hip, and radius fractures. Hip fractures are associated with an 8.4 to 36% excess mortality within 1 year, with a higher mortality in men than in women.⁴  Vertebral compression fractures may result in pain, disability and mortality.  Additionally, wrist or distal radial fractures can interfere with activities of daily living.⁵

ESSENTIALS OF ASSESSMENT

History

Taking a careful patient history with a specific focus on risk factors (see above) is crucial.  Assessment of fall risk is also important. The WHO Fracture Risk Algorithm (FRAX) is a validated tool that can help in patient risk stratification; see Figure 1.⁵  FRAX was developed to calculate the 10-year probability of hip fracture and the 10-year probability of a major osteoporotic fracture.⁵  Another strategy is to use the Osteoporosis Self-Assessment Tool (OST), a simple calculator using age and weight to identify individuals at higher risk of low BMD, see Figure 2. The US Preventative Services Task Force recommends BMD measurement be conducted on any young postmenopausal women who has OST score less than 2, or whose 10-year fracture probability on FRAX is same or greater than that of a 65-year-old white woman without additional risk factors.⁶

Physical examination

The examiner should take careful note of the patient’s body frame, as well as any signs of anorexia, chronic liver disease, alcoholism, and thyroid disease, in an attempt to identify specific secondary, treatable causes of osteoporosis. Skin and facial examinations will help to evaluate for endocrine disorders. Findings compatible with an osteoporotic fracture should be noted. This may include kyphosis and point tenderness over spinous processes for vertebral fractures. Height should be measured annually, preferably with a wall-mounted stadiometer, in postmenopausal women and men older than 50.^5,7

Functional assessment

A thorough functional assessment is essential in evaluating a patient’s fall risk. Some of the most important aspects are a history of falls, muscle weakness, and deficits in gait, balance, or visual acuity. The Timed Up and Go Test (TUG) is a validated instrument that can be used to assess mobility, balance, walking ability and fall risk in older adults.⁸

Laboratory studies

Essential laboratory tests for the initial evaluation of all patients with osteoporosis include a complete blood count, CHEM-7, serum calcium and phosphorus levels, liver function tests, thyroid-stimulating hormone (TSH) level, serum 25-hydroxyvitamin D (25(OH)D) level, and 24-hour urinary calcium. In younger men, total testosterone and gonadotropin levels should be ordered as well. Based on initial lab work results, a number of other tests may be warranted.

Imaging

The American Medical Association (AMA) and the NOF (National Osteoporosis Foundation) recommend a DXA for definitive diagnosis of osteoporosis and for monitoring the effects of therapy.⁵  Current NOF recommendations suggest that the following groups have a DXA scan: all women aged 65 and older and all men aged 70 or older, menopausal and postmenopausal women with risk factors (regardless of age), men aged 50-69 with risk factors, and both men and women who have had broken bones after the age of 50.  DXA scan may also be indicated based on significant height loss and abnormal X-rays of the spine. Vertebral imaging should be considered if a patient has a significant decrease in height to look for compression fractures.⁵

Additional imaging studies include quantitative computer tomography (QCT), peripheral dual-energy X-ray absorptiometry (pDXA), and quantitative ultrasound densitometry (QUS).⁵  Quantitative ultrasound (QUS) is a safe and powerful screening tool for osteoporosis, and it is particularly useful in areas that do not have access to DXA machines. Studies have shown calcaneus QUS is a low-cost and readily-available alternative that is as effective as axial DXA at predicting osteoporosis-related fractures in elderly women; it can be a useful initial screening tool while minimizing exposure to ionizing radiation.⁹  However, QUS devices have not been standardized, and thus, measurements obtained using a particular QUS device should not be compared to those found using a different device.

Supplemental assessment tools

In addition to the initial diagnostic workup for osteoporosis outlined above, a number of other tests may be useful. Causes of secondary osteoporosis may be identified by obtaining parathyroid hormone levels, celiac antibodies levels, serum/urine protein electrophoresis, 24-hour urinary free cortisol, and an overnight dexamethasone suppression test. Biomarkers are a useful tool in detecting bone remodeling.  Resorption biomarkers include serum C-terminal telopeptide (CTx) and urinary N-terminal telopeptide (NTx). Formation biomarkers include serum bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and aminoterminal propeptide of type 1 procollagen (PINP).¹⁰

Early predictions of outcomes

The development of osteoporosis in anorexic females is best predicted by body weight history. Hip fractures have higher mortality rates than other bony fractures, though the risk of mortality significantly decreases with time.  Interestingly, patients with vertebral fractures have an increased risk of mortality even after 1 year has elapsed from time of injury. In women who have had a vertebral fracture, 19% will have another fracture in the next year.¹¹ Serum albumin (a measure of protein intake) has strong prognostic value for survival in patients who have suffered a hip fracture.  Additionally, studies indicate that baseline T-scores at initial assessment are important in determining how often older adults should be screened, with higher scores being associated with a much smaller risk of transitioning to fragility fractures in the immediate future.⁶

Environmental

Evaluating a patient’s home environment and discussing ways to safely maneuver around the home can decrease the risk of falls.  Potential environmental hazards should be discussed with the patient with a focus on practical ways to remove such hazards from the home. The addition of grab bars, shower chairs, and brighter lighting are just some of the modifications that can be done with the help of social work and occupational therapists.

Social role and social support system

Patient, family, and clinician knowledge and awareness of osteoporosis can lead to early detection and diagnosis. Community and family support allows for better access to health care and resources for physical activities, thus decreasing the risk of fractures and complications.

Professional Issues

The physiatrist must always consider osteoporosis as a differential diagnosis for the underlying causes of musculoskeletal conditions in female and elderly patients. Information should be given to a patient diagnosed with osteoporosis regarding prevention of fractures, prevention of falls, and treatment options. Osteoporosis can be treated best with a multidisciplinary team approach including the physiatrist, primary care provider, endocrinologist, physical therapists or personal trainers, as well as the patient’s family and friends.

REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

NOF revised the Clinician’s Guide to Prevention and Treatment of Osteoporosis in 2014, though internationally, many countries or regional medical societies have set up their own protocols.⁵ The American College of Physicians has its own guidelines for the treatment and prevention of low bone mineral density or osteoporosis-related fracture, most recently updated in 2017.⁴ The International Osteoporosis Foundation (IOF) has not endorsed specific guidelines, as emphasis of primary prevention varies across regions.⁵

At different disease stages

Osteoporosis is considered a “silent thief” that is typically asymptomatic until a fracture occurs. During the acute phase of fracture, relieving pain, appropriately stabilizing the fracture, and treating other comorbidities are essential.

NOF suggests pharmacologic treatment in the following groups: patients with a hip or vertebral fracture, patients with a BMD with an associated T-score ≤ -2.5 at either the femoral neck, total hip, or lumbar spine, postmenopausal women and men age 50 and older with low bone mass (T-score between -1.0 and -2.5), and patients with a 10-year major osteoporosis-related fracture probability of ≥ 20% or a 10-year hip fracture probability of ≥ 3% based on FRAX.⁵

The current Food and Drug Administration (FDA) approved first-line pharmacologic agents for the treatment of osteoporosis are bisphosphonates. Alendronate, risedronate and zoledronic acid are all readily available in generic form; ibandronate is rarely prescribes as studies have shown no evidence for reduction of nonvertebral fractures.⁶ Denosumab, raloxifene and calcitonin are other medications that can reduce the risk of fragility fractures. Treatment with teriparatide (an anabolic agent similar to PTH) may also be considered in patients with very high fracture risks or in those who have failed bisphosphonate therapy previously.^5,6 There is a new potential humanized monoclonal antibody called romosozumab, which has been tested in two fracture-endpoint studies and found to be more effective in large increases in BMD in combination with either denosumab or alendronate than denosumab alone.¹²

The effectiveness of treatments should be closely monitored.  Although no standard guidelines exist for monitoring response to treatment, some organizations suggest measuring height annually; obtaining bone turnover markers pre-treatment and every three to six months; and DXA testing should be ordered every two years.⁵ The duration of medication therapy needs to be individualized based on each patient’s osteoporosis risk assessment. Typically, bisphosphonate therapy is three to five years in duration, and teriparatide therapy does not exceed 18 to 24 months.⁵

In addition to this, dietary supplementation with calcium and vitamin D can also aid in decreased the risk of osteoporosis-related fractures. The recommended dietary allowance (RDA) for calcium is 1000mg/day for women ages 19-50 years and increases to 1200mg/day for those 50 years and older; for men, the RDA is 1000mg/day for those ages 19-70 years and increases to 1200mg/day in those 70 years and older. The preferred sources are calcium-rich foods and beverages. The  RDA for vitamin D is 600 IU/day for men and women ages 19-70 years and increases to 800 IU/day for those 70 years and older. These calculations correspond to a serum 25-hydroxyvitamin D level of 20 ng/ml.⁶

Patient & family education

Osteoporosis is a preventable disease. The NOF recommends that postmenopausal women and men age 50 and older be counseled on the risk of osteoporosis and osteoporosis-related fractures.  Recommendations for the general population should include adequate intake of calcium, vitamin D, and vitamin K. Smoking and heavy drinking should be avoided, and risk factors for falls should be reduced. Early identification and treatment of patients with osteoporosis are essential.⁵  

Exercise is approved to prevent and treat the loss of bone mass, help postural stability and the prevention of falls. The exercise types most effective on BMD for the femoral neck appear to be progressive resistance strength training for the lower limbs. The most effective exercise intervention for the spine has been a multicomponent training exercise program with weight-bearing aerobic exercise and training with vibratory platforms.¹³

Emerging/Unique Interventions

Serial central DXA BMD testing is the gold standard for monitoring response to pharmacologic therapy. BMD should be measured 12 to 24 months after initiating or changing therapy and periodically thereafter.⁵

Serially testing bone turnover markers can also be used for evaluating the efficacy of drug therapy. PINP levels should be obtained prior to and 3 to 6 months after the initiation of osteoporosis treatment in order to gauge therapeutic response.¹⁰

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Early identification of patients with osteoporosis and assessing the risks of fracture can reverse bony deterioration and prevent fracture. Screening risk factors and ordering tests for low BMD is crucial to preventing negative outcomes; there is still an estimated 11% of postmenopausal women who have never been screened or never had follow-up counseling and treatment for low BMD.⁴ A multidisciplinary approach and effective communication between the physician and the patient/family lead to better outcomes. Referral to specialists should be strongly considered if the patient has any of the following:

1. Uncontrolled pain (pain medicine specialist)
2. Primary osteoporosis or failure to respond to conventional treatment for osteoporosis (endocrinologist, rheumatologist)
3. Fractures (orthopedist, neurosurgeon)⁴

Special populations

Male adults

Osteoporosis in men remains an underrecognized and undertreated condition.  Loss of bone mass increases in men after age 70 and is often secondary to hypogonadism, corticosteroid use or excessive alcohol use.  Testosterone depletion directly effects both cortical and trabecular bone mass. Elderly men will often present with hip fracture as the first sign of osteoporosis, which is also high risk for developing more fractures in the future if left untreated.¹⁴

Secondary causes of osteoporosis should be considered and corrected, if possible.  Bone mineral density is less helpful in this population, and FRAX should be used to determine whether a specific patient requires treatment.  Treatment options include bisphosphonates, denosumab and teriparatide. Testosterone is not indicated.¹⁴

Pediatrics

Pediatric osteoporosis is defined as having a Z-score < -2, in the presence of clinically significant fracture history. Z-scores of the lumbar spine, hip, and total body are available. Clinically significant fracture is defined as at least one long bone fracture in the lower extremity, at least 2 long bone fractures in the upper extremity, or a vertebral compression fracture. Pediatric osteoporosis may be related to genetic predisposition, calcium or vitamin D deficiency, or a number of other medical conditions (chronic liver disease, burn injuries, malignancies). As with other groups, the prevention and treatment of pediatric osteoporosis should be tailored to the cause of the osteoporosis.¹⁵

Adequate calcium intake and weight-bearing exercises can maximize peak bone mass. The NIH Consensus Conference on Osteoporosis recommends a calcium intake of 800 mg/d until age 10, 1200 mg/d during adolescence, and 1000 mg/d after adolescence. Additional management with bisphosphonates can be helpful, while hormone replacement therapy is not appropriate in this population.¹

Spinal cord injuries

Osteoporosis in spinal cord injury (SCI) occurs predominantly in the lower extremities and pelvis as a result of gravitational unloading and an imbalance between bone formation and resorption.  Bone loss may be enhanced by the lack of muscle traction on bone or by other neural factors associated with SCI. Bone loss begins early after injury, being accelerated in the first six months before stabilizing after 12 months; fractures can occur from low-impact forces that normally would not cause fractures.¹⁶  Prevention is key. To date, bisphosphonates are the best-studied medications for the prevention of demineralization following SCI, and alendronate has been shown to prevent total body and hip bone loss at one year post-injury. Weight-bearing exercises with standing frames and bikes, as well as functional electrical stimulation (FES) have been shown to be effective when started within six weeks of injury.¹⁷

Stroke Osteoporosis after stroke is most often seen in the paretic side, especially in the upper extremities. Bone loss is most significant during the first three to four months following stroke.  The mechanism of post-stroke osteoporosis is thought to be due to a combination of paresis, reduced mobility, side-effects from medications, and nutritional deficits, to name a few. Importantly, stroke patients are at higher risk for fractures due to both an increase in osteoporosis and fall risks. Post-stroke osteoporosis treatments include behavioral/rehabilitative therapy, dietary supplementation, and medications like bisphosphonates.¹⁸

CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Many of the current treatments for osteoporosis have the potential to cause significant adverse effects. Serum estrogen receptor modulators (SERMs) have been linked to endometrial cancer, PTH carries a risk of osteosarcoma, and bisphosphonates can cause osteonecrosis of the jaw (ONJ) and subtrochanteric femoral fractures.⁵

Available treatments have focused on decreasing osteoclast activity, and thus, bone resorption and turnover. Unfortunately, this strategy can affect bone strength and cause a myriad of other side effects after long-term use, some of which have been outlined above.  Future treatments will need to focus on anabolic agents or combined therapy with both anabolic and anti-catabolic agents.

New medications, such as romosozumab are being studied in clinical trials as therapy for osteoporosis. New guidelines regarding exercise in those with osteoporosis have also expanded to include higher intensities and larger volume bone loading with greater safety.

GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

A number of questions regarding osteoporosis are still unanswered: What is the best universally accepted tool to assess bone strength?  Should individuals with family history of osteoporosis be tested earlier than the currently identified timeframes? How can we maximize our peak bone mass when we are young?  Does calcium and vitamin D supplementation truly alter bone quality? How can one best identify and modify risk factors for falling?  What are the long-term adverse effects of the pharmacologic therapies available now?  Further research is needed to answer these and many other questions.

Figure 1

FRAX Clinical Risk Factors

Age Sex Weight Height Previous fracture Parental history of hip fracture Smoking status Glucocorticoid use Rheumatoid arthritis Secondary osteoporosis≥3 units of alcohol/day Femoral neck BMD

 Figure 2

Osteoporosis Self-assessment Tool

Score = [weight (kg) – age (years)] x 0.2

REFERENCES

1. http://www.who.int/chp/topics/Osteoporosis.pdf
2. Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement Online. 2000;17:1-36.
3. http://www.iofbonehealth.org/secondary-osteoporosis
4. Qaseem A, Forciea MA, McLean RM et al. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women:A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med 2017;166(1):818-39.
5. 2014 Clinician’s guide to prevention and treatment of osteoporosis
6. Ensrud KE, Crandall CJ. Osteoporosis. Ann Intern Med 2017;167(3):ITC17-32.
7. http://www.rheumatology.org/I-Am-A/Rheumatologist/Research/Clinician-Researchers/Fracture-Risk-Assessment-Tool-FRAX.
8. Podsiadlo, D. and Richardson, S. The “Timed Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991;39(2):142-148.
9. Hans D, Baim S. Quantitative Ultrasound (QUS) in the Management of Osteoporosis and Assessment of Fracture Risk. J Clin Densitom. 2017;20(3):322-33.
10. Gillian Wheater, Elshahaly M, Tuck SP, Datta HK, and Laar JM. The clinical utility of bone marker measurements in osteoporosis. J Transl Med. 2013; 11: 201
11. Lindsay R, Silverman SL, Cooper C et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001;285(3):320.
12. Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet 2019;393:364-76.
13. Benedetti MG, Furlini G, Zati A et al. The Effectiveness of Physical Exercise on Bone Density in Osteoporotic Patients. Biomed Res Int 2018; Article ID 4840531.
14. Alejandro P, Constantinescu F. A Review of Osteoporosis in the Older Adult: An Update. Rheum Dis Clin N Am 2018;44:437-51.
15. Steffey C. Pediatric Osteoporosis. Pediatr Rev 2019;40(5):259-61.
16. Soleyman-Jahi S, Yousefian A, Maheronnagsh R et al. Evidence-based prevention and treatment of osteoporosis after spinal cord injury: a systematic review. Eur Spine J. 2018;27(8):1798-1814.
17. Weiss D, Kishner S.  Osteoporosis and Spinal Cord Injury    http://emedicine.medscape.com/article/322204-overview
18. Carda S, Cisari C, Invernizzi M, Bevilacqua M. Osteoporosis after Stroke: A Review of the Causes and Potential Treatments. Cerebrovasc Dis 2009; 28:191–200

Original Version of the Topic:

Linqiu Zhou, MD, Anthony Lee, MD. Osteoporosis in Rehabilitation. Publication Date: 2011/11/14.

Previous Revision(s) of the Topic

Linqiu Zhou, MD, Paul Kitei, MD, Chen Zhou, MS-2. Osteoporosis in Rehabilitation. Publication Date: 04/19/2016

Author Disclosure

Nadia Zaman, DO
Nothing to Disclose 

Richard G. Chang, MD, MPH
Nothing to Disclose