Quality in Health

PRACTICE GUIDELINES FOR OSTEOPOROSISNidhi Malhotra and Ambrish Mithal

From the: Department of Endocrinology, Indraprastha Apollo Hospitals,Sarita Vihar, New Delhi 110 044, India.

Correspondence to: Dr. Ambrish Mithal, Senior Consultant, Endocrinology and Diabetes,Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 044. India.

E-mail: ambrishmithal@rediffmail.com

BACKGROUND

1. Osteoporosis is a major public health problem. There israpid increase in aging population in India.

2. Normally one out of two women suffer fromosteoporosis beyond age 50 and one out of 4 havelifetime risk of fractures.

3. Hip fractures are the most devastating consequence ofosteoporosis (20% mortality, another 25% require lifetime assistance). Recent data suggests that multiplevertebral fractures have major impact on the quality oflife, although their overall impact is less than that of hipfractures.

4. In India, recent data indicates that the risk may be evenhigher due to associated nutritional vitamin D andcalcium deficiency [1].

5. Average osteoporotic fractures occur 10-20 years earlierin India, whether this is just related to lower life span isunclear. Earlier diagnosis and treatment can improvemorbidity and mortality.

GUIDELINES ARE DIVIDED INTO 3 GROUPS [2]

(i) Asymptomatic patients who need screening forosteoporosis.

(ii) Patients with definite osteoporosis.(iii) Patients with fracture due to osteoporosis.

KEY EVALUATION

Detailed history to assess risk factors (Table 1) andsecondary causes of osteoporosis (Table 2) should be taken.

Physical examination to rule out spinal abnormalities,fracture and secondary causes is essential.

DIAGNOSIS

Bone Mineral Density (BMD) measurement

Technique

Dual Energy X-ray absorptiometry (DEXA) is preferredas it is quick, has less precision error and less radiationexposure. It is regarded as the gold standard. We classifyaccording to BMD, basically T scores. Since T scores are

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitecturaldeterioration of bone tissue leading to increased bone fragility. The clinical expression of osteoporosis isfracture; osteoporosis is a silent disease till fractures occur.

Table 1: Risk factors for osteoporosis [4,5].

Major Minor

1. Age more than 65 years 7. Female sex2. History of fragility fracture* 8. Late menarche3. Height loss more than 2 cm 9. Early menopause4. Family history of fracture (first degree relative)* 10. Low calcium intake*5. Low body weight (<57kg)* 11. Vitamin D insufficiency*6. Recent weight loss (>5%) 12. Smoking

13. Excess alcohol intake14. Physical inactivity15. Muscle weakness16. Difficulty in getting up from sitting posture*17. Impaired vision and balance18. Long term use of drugs (steroids, antiepileptics, heparin)

*Significant in Indian population.

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population specific, it has been suggested that Indianstandards be used for diagnosing osteoporosis. However,this issue remains unresolved as of date due to lack offracture/ BMD correlation data in Indians. Multiple studiesare underway to find an answer to this question. Thus mostcenters use manufacturer’s standards for the present.

Qualitative Computed Tomography (QCT) is also anaccurate technique to measure BMD, but is not popular dueto high radiation exposure and cost.

Ultrasound based technologies for peripheral bones likethe calcaneum are in wide use throughout India. While inprinciple the technique is approved for screening purposes,lack of standardisation and wide variability among themachines in use in India results in confusion andmismanagement. It is, therefore not the technique of choice.

Other peripheral bone BMD measurement techniques(pDXA, digital radiography) are in limited use and can beconsidered potentially interesting.

What site

Ideally both spine and hip bone density is estimated. Thelowest bone density guides treatment. If one site is selected:

Always do hips in patients over 65 years of age.

Spine should be done in younger population. It is also abetter predictor for therapy assessment.

Management according to bone density

Assess according to T score (Z score is better predictor insecondary osteoporosis and does not correlate with fracturerisk)

T score < 1 SD below mean Normal.

T score > –1 SD but < –2.5 SD OsteopeniaT score > –2.5 SD below mean OsteoporosisT score > –2.5 SD with fractures Severe or established

osteoporosis

1. Guidelines for asymptomatic patients withoutestablished osteoporosis [3].

(a) Postmenopausal Females(b) Premenopausal Females(c) Males

(a) Postmenopausal Women: All postmenopausal women>65 years should routinely undergo a bone density test toassess baseline status. (In case this is not feasible, preventivenutritional and life style measures can be initiated in allindividuals at risk. Those with greater number of risk factorscan be treated more aggressively). BMD measurements inpostmenopausal women <65yrs should be obtained if thereis presence of risk factors (at least 1major or multiple minor)for osteoporosis (Table 1).

(b) Premenopausal Women: BMD estimation is notrecommended routinely, but we should start prevention withcalcium/vitamin D if there is inadequate oral intake / poorsunlight exposure. Risk factors should be assessed(Table 1) hypogonadism and other secondary causes shouldbe looked for (Table 2). One can consider BMD assessmentif multiple risk factors/secondary causes are present.Specific therapy like bisphosphonates is considered only inspecial situations (secondary causes like steroids, organtransplant etc).

(c) Males: Risk factors and secondary causes should beassessed.BMD should be estimated if there is history of fragilityfracture, multiple risk factors or secondary causes.Treat according to guidelines below after complete medicalevaluation (Table 3), if there is evidence of osteopenia orosteoporosis.Testosterone should be given if there is evidence ofhypogonadism.Dopaminergic agonists are to be used if hyper-prolactinemia is present.Bisphosphonates (Alendronate / Risedronate) are first lineof treatment.

Repeat Bone density is recommended every 1-2 years incase of osteopenia or osteoporosis and every 3-5 years ifbone density is normal.

2. Guidelines for patients with establishedosteoporosis

Complete evaluation with history / physical

Table 2: Secondary causes of osteoporosis

1. Hyperthyroidism2. Hyperparathyroidism3. Cushing’s syndrome4. Acromegaly5. Hypogonadism6. Glucocorticoid therapy7. Inflammatory disorders (arthritis, bowel disease,

pulmonary disease)8. Cancer (especially hematological conditions,

multiple myeloma)9. Congenital disorders (osteogenesis imperfecta,

homocystinuria)10. Neurologic disorders (including immobilization and

treatment with antiepileptic drugs)11. Transplantation.

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examination and routine tests to establish the cause ofosteoporosis (Table 3) is recommended.

Ideally we should measure serum calcium, phosphorus,alkaline phosphatase, 25 hydroxy vitamin D levels, intactPTH, spot calcium / creatinine ratio to rule out vitamin Ddeficiency (this is a very high contributor for osteoporosis inIndia). If cost is an issue we can skip these and treatempirically.

If tests indicate vitamin D deficiency and secondaryhyperparathyroidism we treat with high dose vitamin D(calcirol sachet 60,000 units 2-4 times a month) along withcalcium (1000-1500 mg elemental calcium daily).

Repeat serum calcium, alkaline phosphatase at 6 weeksand three months. If cost is not an issue we can repeat PTHand 25 OH vitamin D levels also. We should initiateosteoporosis treatment after normalization of metabolicparameters.

Specific tests to look for secondary causes ofosteoporosis if suspected. i.e., PTH, 24 hr urine calcium,Serum protein electrophoresis, TSH, etc should be carriedout.

If metabolic parameters do not indicate significantvitamin D deficiency, one should start treatment withspecific medication (see drug chart). In generalbisphosphonates like alendronate / risedronate are the mostpowerful agents. Risedronate may produce less GI

intolerance although this is not unequivocally proven.Although unproven in terms of fracture reduction,parenteral bisphosphonates like pamidronate andzolendronate are also options as they produce substantialincreases in BMD.

Raloxifene is a SERM, which provides multiple benefitsto women of postmenopausal age. Although slightly lesspowerful than bisphosphonates, especially with regard tohip fracture reduction, it is a safe and convenient option formany patients.

There is limited role of HRT in light of recent studies. Itmay be used if menopausal symptoms predominate.

Teriparatide (PTH 1-34), an anabolic osteotrophicagent, can be considered in case of severe osteoporosis orfailure of response to bisphosphonates, although there isevidence of attenuation of PTH effect with prior use ofalendronate.

Check bone density every year to follow the treatmenttill it is stable, then do it every 2 years

Consider bone markers (N-telopeptide and osteocalcin) ifneeded to assess early changes during follow-up. These areparticularly useful in steroid induced osteoporosis.

3. Guidelines for a patient with fracture due toosteoporosis

Assess the site of fracture with x-ray.Assess bone density but do not include the fracture site,

as this will give spuriously high results.Assess the severity of pain.Consider narcotics / muscle relaxants if there is severe

pain.Consider calcitonin nasal spray 200 IU daily for 2-3

months for analgesic effect. Higher doses can be used forinitial analgesic effect.

Start usual osteoporosis treatment in combination withcalcitonin.

Teriparatide (PTH 1-34) is the drug of choice in thisgroup followed by bisphosphonates (Alendronate/Risedronate).

After 2-3 months start physical exercise programme andwean off calcitonin.

KEY DO’s

• Always assess all risk factors prior to considering bonedensity.

• If possible repeat bone density at the same place forcomparison purposes.

• During initial evaluation do both hip and spine ifpossible.

Table 3: Evaluation of osteoporosis

To diagnose

• Bone mineral density measurements

To rule out secondary causes of bone loss

Hematological disease and malignancy

• Complete blood count, ESR or CRP, Serumprotein electrophoresis (>50yrs of age).

Chronic Liver Disease

• Liver function tests

Metabolic bone disease

• Serum calcium, phosphorus, Alkalinephosphatase,

• Serum 25 (OH) vitamin D, PTH

Endocrine disease

• 24 hr urine free cortisol, Serum estradiol,Testosterone, FSH, PTH and TSH.

Chronic renal disease and Malabsorption

• Serum creatinine, Endomyseal antibodies toexclude celiac sprue.

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• When starting treatment always give calcium (1200mg/d) and vitamin D (800 IU/d) as part and parcel oftreatment.

• In India it is essential to look for vitamin D deficiency, asit is very common [1].

• Exercise is very important for long-term improvement.Proper education on posture, muscle strengthening andcardiovascular fitness exercise should be given with thehelp of physiotherapist.

KEY DON’Ts

• Do not repeat bone density prior to 1 year of follow up oftreatment.

• The activated forms of vitamin D [1,25 (OH)2 vitamin D(calcitriol) and 1 alpha OH vitamin D] do not haveproven efficacy and can put patients at greater risk ofhypercalciuria and stone formation. These are only to beused in patients with advanced renal disease. If used,proper calcium monitoring is required.

• No exercise should be done during acute stage withfracture.

• Proper instructions to be followed with Alendronate/Risedronate to avoid GI side effects.

DRUG CHART

1. BISPHOSPHONATES

Oral

(a) Alendronate

Use: It is indicated for treatment and prevention ofosteoporosis in both sexes and for glucocorticoidinduced osteoporosis.Dose: 10 mg daily or 70 mg weekly for treatment; 5 mgdaily /35 mg weekly for prevention. It must beadministered with special precautions i.e., it has to betaken empty stomach and upright posture to bemaintained for 45 minutes. One can have only water forthe same period.Adverse effects: Upper GI symptoms, esophagitis,hyper-sensitivity, arthralgiasContraindications: Hypocalcemia, Hypersensitivity,GERD

(b) Risedronate

Use: Same as for alendronate.Dose: 5 mg daily/ 35 mg weekly.Its profile is similar to Alendronate, although there issome evidence of better GI tolerability and rapidantifracture efficacy with Risedronate.

(c) Ibandronate

Use: It has recently been approved by FDA for use inpostmenopausal osteoporosis.Vertebral fracture efficacy is similar to Alendronate andRisedronateDose: 150 mg orally once a month. It requires one hourof fast and upright posture after taking the tablet.Contraindication: Severe renal impairment, hypo-calcemia

Parenteral

(a) Pamidronate

Dose: 30-60 mg IV infusion q 3-4 months

(b) Zolendronate

Dose: 4 mg IV annuallyThere is no fracture data available with the above twobisphosphonates but the BMD results suggest thatefficacy might be comparable to oral bisphosphonates.Flu like reactions are common.

2. SERMS

Raloxifene

Use: Treatment and prevention of postmenopausalosteoporosis.Dose: 60 mg dailyAdverse effects: leg cramps, deep venous thrombosis,hot flushesHip fracture efficacy is not proven yet. It is known toprovide extraskeletal benefits; possible reduction inbreast cancer and CAD events in high risk cases(preliminary data).

3. HRT

Its efficacy is established in treatment of osteoporosisbut it is rarely used now because of adversecardiovascular and breast cancer profile.

4. CALCITONIN

Use: Treatment and prevention of osteoporosis.Dose: Nasal spray 100-200 IU/day.Adverse effects: Hypersensitivity, flushing.It is a weak agent for osteoporosis, but useful in painalleviation following vertebral fracture.

5. PARATHYROID HORMONE

Use: Treatment of severe osteoporosis and gluco-corticoid induced osteoporosisDose: 20-40 mcg subcutaneously daily.Adverse effects: Hypersensitivity, hypercalcemia

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This is a powerful bone forming agent. It producesmarked increases in bone density and reduced fracturerates.

Its use is not recommended beyond 18 months

REFERENCES

1. Arya V, Bhambri R, Godbole MM, Mithal A.Vitamin D statusand its relationship with bone mineral density in healthyAsian Indians.Osetoporosis International 2004; 15:56-61.

2. Mithal A.Position statement on osteoporosis. EndocrineSociety of India, 2004.

3. Raisz L G, Screening for osteoporosis. NEJM 2005; 353:164-171.

4. Jha R M, Mithal A, Edward Brown. Pilot case controlInvestigations of risk factors for osteoporosis in an UrbanIndian Population. 2nd Joint Meeting of the EuropeanCalcified Tissue Society and the International Bone andMineral Society, Geneva, June 25-29, 2005 (Bone Abs).

5. Keramet A, Mithal A, et al (2004). Risk factors forOsteoporosis in urban Asian Indian women presenting for apreventive health check-up. 2nd Joint Meeting of theEuropean Calcified Tissue Society and the InternationalBone and Mineral Society, Geneva, June 25-29, 2005(Bone Abs).