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Board of Officers

10/F Rm. 1002 South Tower Cathedral Heights St. Luke's Medical Center, E. Rodriguez Sr. Ave., Quezon City

Telefax: (632) 725-2133; 723-0101 loc 2002Email: ospfi_secretariat@yahoo.com.ph

Osteoporosis Society of the Philippines Foundation, Inc.

President Vice President

Secretary Treasurer

P. R. O.

Board of Directors

Leilani B. Mercado-Asis, MD, PhD Mary Anne Lim-Abrahan, MDAlejandro V. Pineda Jr., MD Julie T. Li-Yu, MD Miles Francis T. Dela Rosa, MD

Kelvin R. Chan, MD Rodolfo F. Florentino, MDLyndon John Q. Llamado, MD Randy P. Urtula, MD Ditas D. Decena, MD

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OSTAb (screening tool) age

and weight

HIGH risk category?

MEDIUM risk

category?

Refer for CENTRAL DXA measurement OR proceed to treat

Refer for CENTRAL DXA measurement

Preventive measures: nutrition,

calcium, exercise

LOW risk category?

See Figure B

a Postmenopausal women ≥65 y/o Fragility fractures after age 45 BMI <19, weight <120 lbs Men ≥70 y/o Loss of height at least 1.5 inches Secondary causes

b OSTA: Osteoporosis Screening Tool for Asians using age and weight (see attached graph)

At risk for a osteoporosis

1

2

3 4

5 6

7 8

Y

Y

Y

N

N

FiguRE A. Approach to patients who are at risk for osteoporosis

Algorithm to Identify Osteoporosis Case Finding

Updated!

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CENTRAL DXA

measurement a Available?

Request for Thoracolumbar

spine radiograph

Treatment option: bisphosphonates,

calcium/vit D, nutrition, exercise,

prevent falls

"Mod to High risk" from Figure A

1

3

56

7

Y

N

FiguRE B. Approach to patients with central BMD measurementBMD measurement

T-score <-2.5?

T-score bet -1 & -2.5?

(Normal)

Preventive measures: nutrition, calcium,

exerciseRepeat BMD

measurement after 24-36 months

see Figure C

a Gold standard in diagnosis Regions of interest include: lumbar spine, femoral neck, or

ultradistal forearmb Who to treat? BMD < -2 w/ no RF BMD <-1.5 w >1 RF History of fx after age 45

Y

Y

N

N

(Osteoporosis)

(Osteopenia)b

Y

4

2

T-score >-1?

8

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Thoracolumbar spine radiograph

Treatment options: bisphosphonates,

calcium/vit D, nutrition, exercise,

body braces

"Mod to High risk" from Figure A where central

BMD is unavailable

1

2

3

4 5

Y

Y

N

N

FiguRE C. Approach to patients who are at risk but central BMD not availableBMD not available

Any compression fracture/s –

single/multiple vertebrae ?

Any thinning of

trabeculae?

Assurance Preventive

measures: calcium/vit D, exercise

6

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2004 National Guidelines for Oste-oporosis Diagnosis, Prevention and Treatment

Author: Julie T. Li-Yu, M.D., FPCP, FPRA

Abstract

Osteoporosis is considered a major worldwide health problem. Once thought to be part of aging, current evi-dences have considered significant causal relationship between several life style risk factors to its occurrence. Data worldwide has confirmed the considerable increase in occurrence of fragility fractures among patients with osteoporosis. Paucity of national data should not preclude the healthcare policy makers in considering this to cause huge economic burden. The impact of local institutional data to the incidence of the disease should indeed heed a call that something needs to be done at this time to halt the progression of this epidemic.

Currently there is no accurate method of measuring overall bone strength. Since measurement of bone min-eral density, considered a surrogate marker accounting for almost 70% of bone strength, is not widely available nationwide, it is deemed prudent that there should be some sensible ways of identifying high-risk individuals for BMD measurement.

The Osteoporosis Society of the Philippines Foundation, Inc. (OSPFI), a non-stock, non-profit organization and one of the founding members of the Asia Pacific Osteo-porosis Foundation (APOF) presents a set of guidelines intended to help clinicians determine when a bone mass measurement maybe useful in the care of their patient. In areas where central bone mass measurement is not readily available, the use of Osteoporosis Screening Tool for Asians (OSTA) risk index validated in Asian as well as other Caucasian populations using only age and body weight maybe used to determine if a low, medium, or high probability of low bone density exists among postmenopausal women. The goal for the evaluation of patients at risk for osteo-porosis focuses not only on establishment of diagnosis but also to establish fracture risk to be able to make deci-sions regarding the need for instituting therapy. Should patients need anti-resorptive or anabolic agents, there is a need to further monitor changes in bone density, pri-marily to assess therapeutic efficacy of these agents. An increase in bone density, or stabilization of bone density is considered an appropriate surrogate for efficacy of the agent in reducing fracture risk.

Emphasis on preventive efforts at forestalling the deve-lopment of the disease (primary prevention) as well as early detection and treatment or efforts to retard or prevent progression or recurrence of disease (secondary prevention) should be done.

introduction

Osteoporosis is a systemic skeletal disease of compro-mised bone strength leading to an increased risk of fracture. It is considered a global health problem being a major cause of morbidity in the elderly. The fractures associated with osteoporosis cause considerable disa-

bility and loss of quality of life and can be fatal. The annual cost of treating osteoporotic fractures has been estimated to be around $1.2 billion (UK) to $13.8 billion (US). Up to half the bone loss experienced by women is attributable to loss of estrogen. Currently, one in every three women is suffering from this silent disease. Osteoporosis is defined by bone mineral density measurement according to the World Health Organization criteria1:

Normal bone density: T-score* more than and equal to –1

Osteopenia (low bone mass): T-score between –1 & –2.5

Osteoporosis: T-score less than and equal to –2.5

Severe osteoporosis: T-score less than and equal to –2.5 with fragility fracture

impact of Osteoporotic Fractures in the Philippines

In 1995, Department of Health estimated the Filipino elderly population, increasing at the rate of 5.45% per year, is now more than 4 million. In effect, there will definitely be a substantial increase in the incidence of osteoporotic fragility fractures. Among 19,920 patients age 50 years and above admitted at Philippine Ortho-pedic Center (POC) from 1995-1997, majority of them (41%) suffered from femoral fractures, 31% forearm, and 22% had vertebral fractures. Of the 11,354 female patients, 58% of them were reported to have hip fractures2. A similar observation in 1997 disclosed femoral fractures accounted for 53% of all observed fractures3. In a fracture registry done among patients 50 years and above in POC on year 2001, there was an increase in the prevalence of fractures seen on all sites (vertebral, femur, and forearm) compared to years 1999 and 2000. A separate trauma registry compiled from 18 orthopedic training centers all over the Philippines by the Philippine Orthopedic Association (POA) from 2002-2003 reported that a little more than 10% of more than 5000 patients 50 years and above admitted to these hospitals were enlisted to have mixed fractures with more than 70% of them disclosing that these events were precipitated by a fall.

Epidemiology in Asia

Hip Fractures

By the year 2050, it is estimated that 6.4 million people will suffer from hip fracture, with 51% of hip fractures oc-curring in Asia. There is no doubt that certain variations on hip and possibly vertebral fracture incidences occur between different ethnic as well as racial groups, with the highest rate seen among Caucasians, intermediate among Asians, and lowest among Blacks. It was noted by Lau et al in 1985 that hip fracture incidence in Hong Kong women was 4/1000 compared to Caucasian women at 6/1000. There is an actual gradient of hip fracture incidence in Asia, with the incidence being highest in urbanized countries such as Hong Kong and Singapore (see Table 1), where incidence of hip fractures rapidly approach those observed in Caucasian populations. In Hong Kong, as the city underwent urbanization and economic development from 1966 to 1985, the incidence of hip fracture increased by 2.5 fold in women and 1.7 fold

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(preferably L1 to L4), the hip (total, neck, or trochanter), or the forearm (33% radius or one-third radius). Precision varies in different centers worldwide, with approximately 2% in expert centers.

Peripheral Bone Densitometry12

Peripheral devices are useful for assessment of fracture risk. However, clinical utility of peripheral bone densito-meters in the diagnosis of osteoporosis needs to be carefully studied further. Based on the International Society for Clinical Densitometry Position Statement, the World Health Organization (WHO) criteria for diagnosis of osteoporosis and osteopenia should not be used with peripheral BMD measurement other than 33% radius. Different technologies as well as acquisition techniques and reference databases were used in the manufacture of peripheral densitometers limiting their use in the di-agnosis as well as monitoring. They cannot be applied in clinical practice until device-specific cut-points are established.

Bone Turnover Markers

Measurements of bone turnover markers (BTM) can pre-dict future fracture risk. The following biochemical mark-ers of bone turnover can be measured in serum and urine, namely: markers of bone formation, i.e., bone specific alkaline phosphatase, procollagen type I propeptides, osteocalcin and markers of bone resorption, ie. deoxy-pyridinoline cross-links (in urine) and C and N telopeptides of type I collagen cross-link (in both serum and urine).

Both BMD and BTM measurement are related to fracture risk and at the same time, correlate very well with fracture protection13. There is a nonlinear relationship between the magnitude of BMD change and the magnitude of fracture protection14. Biochemical markers can be used to comple-ment BMD testing for assessment of fracture risk.

The Osteoporosis Society of the Philippines Founda-tion, Inc. (OSPFI), a member society of the International Osteoporosis Foundation (IOF) and a founding member of Asia Pacific Osteoporosis Foundation (APOF) recom-mends the following clinical guidelines on the indications for bone densitometry:

• all postmenopausal women >65 years of age regard-less of risk factors

• all postmenopausal women ≤65 years, in the presence of 1 or more risk factors for osteoporosis

• all postmenopausal women who are considering therapy for osteoporosis if BMD test would facilitate such a decision

• all postmenopausal women on prolonged hormonal replacement therapy

• all postmenopausal women and men who have had a

in men6. If similar increases occur in other countries in Asia, including the Philippines, the burden of hip fracture will be tremendous, with the incidence rapidly approach-ing or even surpassing the Caucasian figures.

Vertebral Fractures

Vertebral fractures are associated with height loss, back pain, functional impairment, kyphosis, and reduced qua-lity of life. The risk of new vertebral fracture increases with age and is elevated in patients with existing vertebral fractures or low bone mass. Elevations in fracture risk in patients with prevalent vertebral fractures are apparent within 1 year after the first incident fracture and increase with the number of prevalent fractures. Prevalence of vertebral fracture varies according to popu-lation sampled as well as diagnostic criteria used. Some large scale studies have actually pointed out that the frequency of vertebral fractures might actually be higher in Asians than in Caucasians (30% in Hong Kong Chinese women7 as compared to 26% in American Caucasians8). The high prevalence of vertebral fracture was subse-quently collaborated in studies conducted in Beijing, China9 and in Taiwan10. Though no further epidemiologic studies were conducted in other parts of Asia, it is still considered a prevalent health problem that will likely increase exponentially as the Asian population ages.

Risk Factors

Established risk factors for osteoporosis are grouped into major categories: age, or age-related; genetic; environmental; estrogen/androgen deficiency and chronic diseases; and physical characteristics of bone. These risk factors cannot, however, replace BMD measurements in predicting fractures, but rather identify high risk group of individuals who should undergo dual x-ray absorptiometry (DXA) examination and screening. Of the different deter-minants of bone strength, only BMD and bone turnover can be measured in patients with or at risk for osteoporo-sis. There is good correlation between BMD and fracture risk among Caucasians as well as study done in Hong Kong Chinese7. Each standard deviation reduction in femoral neck BMD increases the age-adjusted risk of hip fracture by a factor of 2 8, 11.

Diagnosis

Techniques for Measuring BMD12

Since bone strength reflects bone density and bone quality, bone mineral density (BMD) has been the stan-dard measurement for diagnosing osteoporosis. Central DXA is currently considered the “gold standard” for the diagnosis of osteoporosis. Skeletal sites for BMD mea-surement to include the regions of interest are the spine

Table 1. Incidence of hip fracture in 5 Asian countries (adjusted to and presented with US Caucasian figure)

Hong Kong Singapore Malaysia Thailand uS

Women 459 442 218 269 535

Men 180 164 88 114 189

Results were from the Asian Osteoporosis Study4 and were adjusted to the 1989 US white population5

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µg/day of vitamin D for men and women over the age of 50. Clinicians should advise patients to maintain an adequate intake of calcium and to enjoy moderate sun exposure to promote the synthesis of vitamin D.

2. Perform regular load-bearing activity22

Exercise and activity program are only one compo-nent of a comprehensive program for the prevention of osteoporosis. Exercise benefits include: decreased risk of falling, improved bone mass and strength, enhanced muscle strength, improved balance, better posture, increased flexibility of soft tissues and better range of motion, improved cardiovascular fitness, improved depression, and generally, a better overall quality of life.

3. Smoking cessation23

Excessive bone loss occurs in smokers. Smoking has been reported to impair osteoblast or bone forming cells function, resulting to early menopause, lower body weight, and lower estrogen levels. Poor calcium absorption found in postmenopausal women who smoke is caused by decrease in serum PTH lead-ing to decreased renal hydroxylation of 25(OH)D to calcitriol.

4. Avoid alcoholism24

Alcohol consumption has also been associated with osteoporosis. There has been reports on the dose-response relationship demonstrated between the average number of drinks per day and age-adjusted bone density in premenopausal women.

5. Fall prevention25

Walking aids, such as canes and walkers, allow continued independent mobility in many elderly pa-tients, but must be used to avoid falls during use. Hip strengthening exercises and the slow movement martial arts exercise, Tai Chi, have been shown to improve several physical performance measures and psychosocial indicators as well as lowering the risk of falls by 40%.

6. Hip protectors26,27

Hip protective pads, worn in side pockets of stretchy undergarments, protect against hip fractures in an elderly nursing home (average 81 years old) popu-lation. While regular use and compliance is another issue, these devices are considered for elderly indi-viduals at risk for hip fracture.

Pharmacologic Agents

Osteoporosis can be treated with antiresorptive and ana-bolic agents, which are effective in reducing fracture risk. Pharmacologic agents work by preventing further bone loss or increasing bone mass. Antiresorptive therapies are important aid in treating and preventing osteoporosis because of their low incidence of side effects, good safety profile, and proven efficacy.

It is recommended that women and men who sustained hip fracture, incident vertebral fracture, or other estab-

fracture of any type as an adult after 45 years of age• all men ≥70 years of age• maternal history of hip fracture after 45 years of age• loss of height (at least 1.5 inches), thoracic kyphosis• low body weight (<120 lbs)• radiographic evidence of low bone mass &/or vertebral

compression deformity• conditions associated with low bone mass

- Prolonged corticosteroid use (>7.5 mg/day for 3 months or more)

- Cushing’s syndrome - Eating disorder – anorexia nervosa - Hyperthyroidism - Prolonged immobilization - Inflammatory arthropathies – rheumatoid arthritis,

ankylosing spondylitis - Gastric surgery, malabsorption syndrome - Premature menopause, hypogonadism

Because of paucity of data, indications for bone densito-metry is not routinely recommended for premenopausal women, children between 5-12 years and adolescents 13-19 years of age. The diagnosis of osteoporosis on these groups of individuals should not be made solely on densitometric criteria alone. Every effort should be done to optimize the lifestyle modification of these individuals in order to attain a good quality peak bone mass15.

In a developing country like ours where access to central BMD measurements is limited, simple questionnaires have been designed to help target high-risk women for BMD measurements, thereby avoiding the cost of meas-uring women at low risk16. Numerous risk factors were collected from postmenopausal women in eight Asian countries evaluating their ability to identify women with os-teoporosis defined by femoral neck BMD T-scores ≤2.5. The Osteoporosis Screening Tool for Asians (OSTA) risk index had a sensitivity of 87%-91% and specificity of 45%-67% which was similarly validated in Japan17, Korea18, and other Caucasian populations (See Appendix). This tool, based only on age and body weight, performed well for classifying the risk of osteoporosis among post-menopausal Asian women19 and applying it would result in more prudent use of BMD technology.

Prevention and Treatment

Preventing the first fracture is critical to maintaining skel-etal health and integrity and avoiding the cascade of fur-ther bone loss and fractures that characterize advanced disease. Prompt identification and treatment of patients at risk for osteoporosis can prevent fractures and their accompanying pain, disability, and financial burden. Primary Prevention of Osteoporosis The following are considered main components for the primary prevention of osteoporosis:

1. Maintain an adequate calcium and vitamin D intake20,21

Calcium is the nutrient most important for attaining peak bone mass and for preventing and treating post-menopausal osteoporosis. The Food and Nutrition Research Institute (FNRI-DOST) of the Philippines recommends 800 mg/day of calcium and 10-15

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found that 5 years of HRT reduced the risk of clinical vertebral fractures and hip fractures by 34%, with an associated increase in risk of myocardial infarction, in-vasive breast cancer, pulmonary emboli, and deep vein thrombosis. Non-estrogen drug treatments are preferable to estrogen therapy, if drug treatment is considered solely for the prevention of osteoporosis.

Tibolone

Tibolone is a synthetic progestin that does not stimulate the endometrium in contrast to conventional HRT prepara-tions. It is a tissue specific regimen that exerts beneficial effects on the bone, as well as on climacteric symptoms, via direct activation of estrogen receptor. In a 10-year non-randomized prospective study42, tibolone had significantly increased the mean bone mineral density in the lumbar spine and femoral neck by 4.8% and 3.7% respectively, compared with baseline. In a separate observational study done43, there was a mean increase of 4.1% in spinal BMD and 1.6% in hip BMD at 8 years compared to baseline measurements.

Calcitonin

Thus far, only one large trial has been conducted which showed that calcitonin at 200IU intranasal daily for 5 years could lower vertebral fracture risk by 21%44. How-ever, there is no evidence that calcitonin decreases other non-vertebral fracture rate, hence, it should not be con-sidered as first line drug for the treatment of osteoporosis. On the other hand, calcitonin has a well-documented analgesic effects which is particularly interesting in the weeks following the occurrence of a vertebral fracture.

Vitamin D

Vitamin D3 (cholecalciferol) supplementation with cal-cium administered orally for 18 months resulted to 50% reduction in non-vertebral fracture rates45 and a 25% reduction in non-vertebral and hip fracture rates46. The indicator for determining adequacy of vitamin D intake is serum 25(OH)D which sums up the total production of cutaneous vitamin D and the ingested oral vitamin D2 or D3. To date, there are no studies on serum con-centration of 25(OH)D among Filipinos. In the absence of concrete data on which adequate intakes of vitamin

lished osteoporotic fractures, postmenopausal women with BMD T-score ≤ - 2.0 with or without risk factors, those with T-score ≤ -1.5 in the presence of one or more risk factors, and those who belong to the high risk category using OSTA should receive drug treatment.

Bisphosphonates

Bisphosphonates offer excellent tolerability and protec-tion from both spine and hip fractures in patients with osteoporosis. These agents, which include alendronate and risedronate, significantly reduce bone loss, and their effects can be observed quickly. Bisphosphonates are the only agents in prospective clinical trials that have been shown to reduce the risk of hip and other nonver-tebral fractures28,29. Alendronate and risedronate should be considered as first line drugs for preventing fractures in osteoporotic patients. In patients with prior vertebral fractures, alendronate (10 mg daily for 3 years) and rised-ronate (5 mg daily for 3 years) have shown reduction in risk of new vertebral fractures by 20%30 and 65%31 respectively and hip fracture by 55%32. Ten year admin-istration of alendronate data shows continued increases in BMD, 13.8% at the spine and between 5-6% at the hip33. New generation of bisphosphonates are currently undergoing intensive studies which may provide different options, such as route of administration and tolerability profiles. (see Table 2)

Selective Estrogen Receptor Modulators

In randomized controlled trials (RCT), raloxifene (60 mg oral daily for 2 years) has been shown to increase BMD in postmenopausal women, but less than those reported for bisphosphonates and estrogen. It is associated with a significant reduction in the risk of vertebral fractures38,39. However, non-vertebral fractures were not measured in these studies. Though there is a risk reduction in breast cancer and reduction in total cholesterol with the use of raloxifene, there is an associated increase in hot flushes and deep venous thrombosis.

Hormonal Replacement Therapy

Estrogen therapy reduces bone loss for 10-15 years after menopause, with increase in BMD averaging 5% over 3 years40. The Women’s Health Initiative41 report

Table 2. Major fracture prevention randomized controlled trials with anti-resorptive agents in postmenopausal women with osteoporosis

Trial Drug Prior vertebral Duration Vertebral fracture Hip fracture fractures (years) reduction reduction (% reduction) Liberman25 1995 ALN >50% 3 48% —** Black26 1996 ALN 100% 3 47% 51% Cummings27 1998 ALN 0 4.2 44% 21% Bone28 2004 ALN 17.5-30.8% 10 similar to —** Liberman Harris29 1999 RIS 65% 3 41% —** Reginster30 2000 RIS 100% (all had 3 49% —** at least 2 fractures) McClung31 2001 RIS 38% 3 40%* 30% Watts32 2003 RIS 68% 1 62% —**

* not assessed in all patients ** not measured

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by measurement of bone mineral density, preferably when subjects are commencing CS treatment or soon after. From a clinical standpoint, the optimal approach is primary prevention in patients commencing CS who have not yet lost bone, however, treatment (or secondary prevention) in patients on chronic CS, who will almost certainly have some significant degree of existing bone loss, will also reduce fracture risk. Important approaches to GIOP include: Use the lowest CS dose possible since bone loss is dose dependent, use of agents that prevent or reverse bone loss. Agents that have been investigated in several large double-blind randomized trials include calcium, vitamin D and its metabolites, calcitonin, hormone therapy, bisphosphonates55,56,57, and PTH.

Monitoring

Changes in bone density account for only a fraction of the fracture protection afforded by antiresorptive therapy. For various antiresorptive drugs13,58,59, the proportion of fracture risk reduction explained by changes in BMD in response to therapy varies. The amount of increase in bone density in response to therapy is not indicative of the amount of fracture protection gained. Comparisons of anti-fracture effectiveness between agents cannot be based on differences in response to BMD or BTM across clinical trials.

Measurement of BTM maybe a helpful tool in monitoring response to therapy. In elderly patients, high bone turno-ver marker levels have been shown to predict hip fracture in an independent and complementary way to bone mineral density. The rapid reduction in bone turnover that occurs when antiresorptive therapy is begun corre-sponds in time with the rapid reduction in spine fracture risk seen with treatment. Risedronate therapy reduces bone forming marker by approximately 22% and bone resorbing marker by 44% after 24 months of treatment60 while alendronate decreases BTM by 40-50% after 3 to 6 months of treatment61.

A clinician tasked to monitor response of patients with osteoporosis to treatment should be able to focus on three (3) important objectives: 1st, to evaluate efficacy of therapy in relation to fracture prediction since the primary goal of therapy is to reduce fracture risk; 2nd, to identify non-responders because these patients will require a change in treatment course; 3rd, to enhance adherence to long-term treatment program for maximum benefit.

One important purpose of monitoring therapy is to iden-tify non-responders-patients who display a deterioration of skeletal health while on treatment. No change in BMD or BTM while on treatment does not equate to non-response. A definite loss in BMD, as seen in BMD changes greater than the least significant change, is a signal to review dosing and compliance and to look for other contributory factors that would undermine or minimize therapeutic effect (eg. vitamin D deficiency). Typically one year after initiation or change of therapy is appropriate, with longer intervals once therapeutic effect is established. In conditions where there is an associated rapid bone loss, more frequent monitoring will be appro-priate57. Intervals between BMD test should therefore be determined according to each patient’s clinical status as well as cost-benefit analysis of doing one.

D for Filipinos can be based, the 2002 Recommended Energy and Nutrient Intakes (RENI) Committee adopts the recommendations from World Health Organization and international advisory bodies 20.

Calcium

Calcium has been used as adjunctive therapy in most cli-nical trials on antiresorptive agents; and calcium supple-mentation should be prescribed with such therapies. Its use as a monotherapy is insufficient to prevent fractures in osteoporotic patients. Results of controlled trials dem-onstrated that calcium as a monotherapy increased BMD by 1-2% over 2-3 years, this produced small though statistically significant reduction in fracture incidence.

Bone Forming Agents: Parathyroid Hormone (PTH), Strontium Ranelate

PTH is an anabolic agent which substantially increases bone density and reduces the incidence of vertebral and non-vertebral fractures. A recent large clinical trial showed that PTH (20 µg SQ per day for 18 months) in-creased the vertebral BMD by 9% and femoral neck BMD by 3%. Such therapy likewise reduced vertebral fracture risk by 65% and non-vertebral fracture risk by 55% after 18 months of therapy47. Recent study on its administration with bisphosphonate (alendronate) did not show additional benefit over PTH alone48,49. The effect of 2 g/day of strontium ranelate on non-ver-tebral fracture showed a significant reduction in relative risk of experiencing a first non-vertebral fracture when compared to placebo in an intention to treat population. A 41% reduction in the relative risk of experiencing hip fracture was demonstrated in the population having regularly taken strontium ranelate for the first 18 months of the study50,51.

Drug Therapy for Osteoporosis in Men

A. Alendronate52

Results in 2 studies in men showed that the alendronate (10 mg orally daily for 2 years) increased lumbar spine BMD by approximately 5.3% with significant reduction in incidence of vertebral fracture observed in both stud-ies.

B. Testosterone53,54

Results of clinical trials showed that testosterone therapy increased BMD by a range of 1-5% in men with or without hypogonadism. Larger and well designed trials on the effects of testosterone are still lacking.

glucocorticoid induced Osteoporosis (giOP)

Corticosteroids are widely used since they are considered effective agents for control of many systemic inflamma-tory disorders. Hypercalciuria develops and bone loss occurs quickly within the first 6-12 months of initiation of corticosteroid therapy, thereafter, the rate of bone loss slows to 2-3 times that of normal. The risk of corticoster-oid-induced osteoporosis increases as the cumulative corticosteroid dose increases. Assessment of fracture risk with corticosteroid (CS) is currently best performed

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antiresorptive drugs. Am J Med. 2002;112:281-289 14. Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD.

Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003;18:1051-1056

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17. Fujiwara S, Masunari N, Suzuki G, et al. Performance of osteoporosis risk indices in a Japanese population. Curr Ther Res 2001;62:586-594

18. Park HM, Sedrine WB, Reginster JY, Ross PD. Korean experience with the OSTA risk index for osteoporosis. J Clin Densitom 2003;6:247-250

19. Koh LKH, Sedrine B, Torralba TP, Kung A, et al. A simple tool to identify Asian women at increased risk of osteoporosis. Osteoporosis Int 2001;12:699-705

20. Recommended Energy and Nutrient Intakes Philippines (RENI), 2002 Edition

21. Reid IR, Ames RW, Evans MC, et al. Effect of calcium supplementation on bone loss in postmenopausal women. N Engl J Med 1993;328:460-464

22. Wolff I, Croonenborg J, Kemper H, et al. The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in pre- and postmenopausal women. Osteoporosis Int 1999;9:1-12

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24. Holbrook TL, Barrett-Connor E. A prospective study of alcohol consumption and bone mineral density. Br J Med 1993;306:1506-1509

25. Tinetti ME, et al. A multifactorial intervention to reduce the risk of falling among elderly people living in the community. N Engl J Med 1994;331:821-827

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27. Ekman A, Mallmin H, Michaelsson K, Ljunghall S. External hip protectors to prevent osteoporotic hip fractures. Lancet 1997;350:563-564

28. Boonen S, Brandi MI, Harrington T, et al. Risedronate reduces the risk of non-vertebral fracture in osteoporotic postmenopausal women as soon as 6 months. (Abstract) Osteoporosis Int 2002;13:515

29. Black DM, Thompson DE, Basuer DC, et al. Fracture risk reduction with alendronate in women with osteoporosis : the fracture intervention trial. J Clin Endocrinol Metab 2000;85:4118-4124

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31. Watts NB, Josse RG, Hamdy RC, Hughes RA, et al. Risedronate prevents new vertebral fractures in postmenopausal women at high risk. J Clin Endocrinol Metab 2003:88;542-549

32. McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med 2001;344:333-340

33. Bone HG, Hsoking D, Devogelaer JP, Tucci JR, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. New Engl J Med 2004;350:1189-1199

34. Liberman UA, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995;333:1437-1443

35. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low density but without vertebral fractures. JAMA1998 ;280:2077-2082

36. 34. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. JAMA 1999;282:1344-1352

37. Reginster J-Y, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporosis Int 2000;11:83-91

38. Kanis JA, Johnell O, Black DM, et al. Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcome of Raloxifene Evaluation trial. Bone 2003;33:293-300

39. Maricic M, Adachi JD, Sarkev S PhD, et al. Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. Arch Intern Med 2002;162:1140-1143

40. Writing group for the PEPI trial. Effects of hormone therapy on bone mineral density. JAMA 1996;276:1389-1396

41. Writing Group for Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized

Recommendations on when to repeat BMD measurement

Postmenopausal women or elderly men with normal baseline BMD: repeat at least after 2-3 years

Postmenopausal women or elderly men on treatment: repeat at least after 1-2 years

Patients on corticosteroid therapy (>7.5 mg/day for at least 3 months): repeat every 6 months

Summary

In summary, the OSPFI strongly recommends indi-vidualized approach to screening for osteoporosis. Though there is a universal recognition on high-risk patient profile for osteoporosis, clinicians need to be aware of the importance of bone density test in screen-ing asymptomatic individuals and utilizing central bone mineral density measurement as a valid way of evaluating patients with fragility fracture or have a disease, condition, or medication associated with osteoporosis. Also, general care practitioners as well as specialists should fully utilize the OSTA as part of their initial evaluation in identifying patients who are at low, intermediate, or high risk for osteoporosis, and measure BMD when appropriate, before fractures occur. Lastly, primary prevention should still be the forefront of our general medical care in the community, focusing on measures to build good quality bone mass. Patients who are identified to be osteoporotic deserve secondary and tertiary preventive measures to prevent fractures and its complications.

References:

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2. Dela Rosa M. Philippine Orthopedic Hospital 1995-1997: Personal Communication

3. Fractures at the UST Hospital, Clinical Division: Group XI: A 1992-1996 Survey; UST Hospital Annual Intern’s Scientific Paper Presentation, 1997.

4. Lau EMC, Lee JK, Suriwongpaisal P, et al. The incidence of hip fracture in four Asian countries: The Asian Osteoporosis Study (AOS). Osteoporosis Int 2001;12:239-243

5. Ho SC, Bacon WE, Haris T, Lorker A, Maggi S. Hip fracture rates in Hong Kong and the United States, 1988 through 1989. Am J Public Health 1993;83:694-697

6. Lau EMC, Cooper C, Wickham C, Donnan S, Barker DJP. Hip fracture in Hong Kong and Britain. Int J Epidemil 1990;19(4):1119-1121

7. Lau EMC, Chan HHL, Woo J, et al. Normal ranges for vertebral height ratios and prevalence of vertebral fracture in Hong Kong Chinese: A comparison with American Caucasians. J Bone Miner Res 1996;11:13 64-1368

8. Black DM, Cummings SR, Stone K, Hudes E, Palermo L. Steiger P. A new approach to defining normal vertebral dimension. J Bone Miner Res 1991;6:883-892

9. Xu L, Cummings SR, Mingwei Q, et al. Vertebral fractures in Beijing, China: The Beijing Osteoporosis Project. J Bone Miner Res 2000;15:2019-2025

10. Tsai KS, Twu Sj, Chieng Pu, et al. Prevalence of vertebral fractures in Chinese men and women in urban Taiwanese communities. Calcif Tissue Int 1996;59:249-253

11. Black DM, Cummings SR, Melton III LJ. Appendicular bone mineral density and a woman’s lifetime risk of hip fracture. J Bone Miner Res 1992;7:639-646

12. Leib ES, Lewiecki EM, Binkley N, Hamdy RC. Official positions of the International Society for Clinical Densitometry. J Clin Densitom 2004;7:1-6

13. Cummings SR, Karpf DB, Harris R, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with

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controlled trial. JAMA 2002;88(3):321-333 42. Rymer J, Robinson J, Fogelman I. Ten years treatment of tibolone 2.5

mg daily: effects on bone loss in postmenopausal women. Climacteric 2002;5:390-398

43. Prelevic GM, Markou A, Arnold A, Bartram C, et al. The effect of tibolone on bone mineral density in postmenopausal women with osteopenia or osteoporosis – 8 years follow-up. Maturitas 2004;47:229-234.

44. Chestnut CH, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med 2000;109(4):267-276

45. Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementatio on bone density in men and women 65 years of age or older. New Engl J Med 1997;337:670-676.

46. Chapuy MC, Arlot ME, Duboeuf J Brun, et al. Vitamin D and calcium to prevent fractures in the elderly. New Engl J Med 1992;327:1637-1642

47. Neer RM, Aravaud CD, Zanchetta JR, et al. Effect of PTH (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434-1441

48. Finkelstein JS, Hayes A, Hungelman JL, et al. The effects of PTH, alendronate, or both in men with osteoporosis. New Engl J Med 2003;349:1216-1226

49. Black D, Greenspan SL, Ensreed KE, et al. The effects of PTH and alendronate alone or in combination in postmenopausal osteoporosis. New Engl J Med 2003;349:1207-1215

50. Meuier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. New Engl J Med 2004;350:459-468.

51. D’Haese PC, Santacruz F, De Broe ME, et al. Postmenopausal osteoporosis and strontium ranelate. New Engl J Med 2004;350:2001-2003.

52. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000;343:604-610

53. Katznelson L, Finkelstein JS, Schoenfeld DA et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996;53:18-23

54. Francis RM. The effects of testosterone on osteoporosis in men. Clin Endocrinol 1999;50:411-414

55. Saag K, Emkey R, Schnitzler TJ, et al. Alendronate for the prevention and treatment of glucocorticoid induced osteoporosis. N Engl J Med 1998;339:292-299

56. Stanley-Cohen S, Levy RM, Keller M, et al. Risedronate therapy prevents corticosteroid-induced bone loss. Arthritis Rheum 1999;42:3209-3218

57. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 2001;44:1496-1503

58. Watts N, Lindsay R, Barton IP, et al. Only a small proportion of vertebral fracture risk reduction is explained by BMD increases (abstract). International Society of Clinical Densitometry Annual Meeting: January 30, 2004;Miami Fla. Poster 135

59. Sarkar S, Mitlak B, Wong M, Stock JL, et al. Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 2002;17:1-10

60. Fogelman I, Ribot C, Smith R, Ethgen D, et al. Risedronate reverses bone loss in postmenopausal women with low bone mass: Results from a multinational, double-blind, placebo controlled trial. J Clin Endocrinol Metab 2000;85:1895-1900

61. Devogelaer JP, Broll H, Correa-Rotter R, et al. Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis. Bone 1996;18:141-150

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• If you are in the yellow or red region of the chart above, your risk of osteoporosis may be increased. • If you have broken any bones after menopause, your risk is increased regardless of your current age and weight. • Other factors can also increase your risk, such as corticosteroid use (losses increase with dose and duration), hypogonadism, immobilization (bed-

ridden, casted fractures, wheelchair-bound, etc.) low body weight, poor nutrition especially calcium, smoking, sedentary lifestyle, endocrine disorders (hyperthyroidism, hypercortisolism, hyperparathyroidism) and caffeine use.

• A bone density test can help your doctor confirm a diagnosis of osteoporosis, even before broken bones happen. Most methods for measuring bone mineral density are fast, safe and painless.

Laboratory tests useful in ruling out secondary causes of osteoporosis, as reflected by high Z-scores on BMD

CBC, TSH, testosterone in men, serum calcium, alkaline phosphatase, serum and urine protein electrophoresis, liver function tests, creatinine, 24-hour urinary calcium

Medical conditions that maybe associated with an increased risk of osteoporosis (NOF guidelines 2002)

AIDS/HIV Amyloidosis Ankylosing spondylitis Chronic obstructive pulmonary diseaseCongenital porphyria Cushing’s syndrome Eating disorders (eg. anorexia nervosa)Female athlete triad Gastrectomy Gaucher’s disease Hemochromatosis

Hemophilia Hyperparathyroidism Hypogonadism, 1o and 2o (eg. amenorrhea) Hypophosphatasia Idiopathic scoliosis Inadequate dietInflammatory Bowel DiseaseInsulin-dependent Diabetes MellitusLymphoma and leukemiaMalabsorption syndromesMastocytosis

Multiple myelomaMultiple sclerosisPernicious anemiaRheumatoid arthritisSevere liver disease, esp. PBCSpinal cord transsectionSprueStroke (CVA)ThalassemiaThyrotoxicosisTumor secretion of PTHrPWeight loss

Appendix

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BiphosphonatesAlendronate FosamaxAlendronate/Cholecalciferol FosavanceIbandronic acid BonvivaRisedronate Actonel Actonel 35 mgZoledronic acid Aclasta

Calcium-Regulating DrugsTeriparatide ForteoSynthetic salmon Calcitonin Miacalcic

Calcium Supplements Calci-Aid Calsan Drugmaker's Biotech Calcium carbonate Rhea Calcium Lactate Tums United Home Calactate

Calcium Supplements with Vitamn D Agre-Calvit (Reformulated) Calciday Calcinature Osteofos

Estrogens, Progesterones & Related Synthetic Drugs

Estradiol Climara Estrofem ProgynovaEstradiol/ Cyproterone acetate

Climen 28Estradiol/Drospirenone AngeliqEstradiol/Dydrogesterone FemostonEstradiol/Norethisterone Kliogest TrisequensEstrogen-Conjugated PremarinEstrogen-Conjugated/Medroxyprogesterone acetate Premelle 2.5/Premelle 5 Premelle Cycle 5Tibolone Livial

Nutritional Products Anchor Shape-up Non-fat Milk Powder Anlene Active Hi-Calcium Non-fat Milk Powder

Anlene Active Hi-Calcium Reduced Fat Milk Powder Chocolate Flavour Anlene Active Hi-Calcium

UHT Anlene Gold Hi-Calcium Non-

fat Milk Powder Anlene Gold Hi-Calcium Non-

fat Milk Powder Chocolate Flavour

Anlene Gold Hi-Calium UHT Anlene Plus Hi-Calcium Non-fat Milk Powder Athena Hi-Calcium Non-fat Milk for Women Calciumade Nestle Calcium Plus w/ Fiber

Sustagen Premium Procalcium Selective-estrogen receptor modulatorRaloxifene Evista

TestosteroneTestosterone undecanoate Andriol Testocaps Nebido Vitamin D & Derivatives Rhea Vitamin A and DCalcitriol Rocaltrol

Other Drugs Affecting BoneStrontium ranelate Protos

Recommended Therapeutics

The following index lists therapeutic classifications as recommended by the treatment guideline. For the prescriber's reference, available drugs are listed under each therapeutic class. For drug information, please refer to the Philippine Drug Directory System (PPD, PPDr, PPD Text, PPD Tabs).