Osteoporosis

Abstracts

A osteoporose é uma doença ósteo-metabólica que atinge especialmente mulheres após a menopausa. Segundo a Organização Mundial de Saúde 1/3 das mulheres brancas acima dos 65 anos são portadoras de osteoporose. Entretanto estima-se que um homem branco de 60 anos tenha 25 % de chance de ter uma fratura osteoporótica. O diagnóstico e planejamento terapêutico são baseados na densitometria óssea e na dosagem laboratorial dos marcadores de formação e reabsorção óssea. A densitometria também é o melhor preditor de fraturas. Os medicamentos atualmente disponíveis atuam mais na inibição da reabsorção óssea. A principal forma de tratamento da osteoporose é a prevenção: deve-se evitar o fumo; álcool e café devem ser consumidos com moderação; a atividade física e ingestão adequada de cálcio são fundamentais; o treinamento proprioceptivo pode colaborar para prevenir quedas e, conseqüentemente, as fraturas.

Osteoporose

ARTIGO DE REVISÃO

Osteoporosis

Julio Cesar Gali

Medicine Doctor, University of São Paulo College of Medicine

Physician, Orthopedics and Traumatology Service, Medical and Biological Sciences Center, PUC-SP

^{Correspondence}

SUMMARY

Osteoporosis is an osteometabolic disease affecting mainly postmenopausal women. According to the World Health Organization, 1/3 of older than 65 white women are affected by osteoporosis. Notwithstanding, the estimates say that 60-year old white males have a 25% chance of osteoporotic fractures. Diagnosis and the therapeutic design are based on bone densitometry and laboratory determinations of formation and bone reabsorption markers. Densitometry is the best fracture predictor. Currently available drugs act inhibiting bone reabsorption. The main form of treatment of osteoporosis is prevention: smoking must be avoided; alcohol and coffee drinking must be moderate; physical activity and adequate calcium intake are fundamental; proprioceptive training can prevent falls and, consequently, fractures.

Key Word: Osteoporosis.

CONCEPT

Osteoporosis is a progressive systemic disease characterized by diminution of bone mass and deterioration of the microarchitecture, causing bone fragility and increasing the risk of fractures.

Physiologically, bone deposition by osteoblasts is continuous and bone absorption occurs where the osteoclasts are active. Except for growing bones, there is an equilibrium between bone deposition and bone absorption; in osteoporosis, the osteoblastic and osteoclastic activities are disproportionate, and the latter predominates.

The skeleton accumulates bone until the age of 30, and bone mass is greater in males than in females. After 30, a 0.3% yearly loss occurs. In women, loss is greater during the 10 first post-menopausal years, and it can reach 3% a year. Sedentary women lose more bone⁷.

Osteoporosis is a common condition. According to the World Health Organization criteria, 1/3 of the white women older than 65 present osteoporosis²¹; it is estimated that osteoporotic fractures will occur in about 50% of the women older than 75 years²⁰.

Though osteoporosis is less commom in men, it is estimated that about 1/5 to 1/3 of hip fractures are observed in men and that 60 year-old white men have a 25% probability to have fractures due to osteoporosis¹².

CLASSIFICATION

Osteoporosis is primary (idiopathic) or secondary. Primary osteoporosis can be type I and type II.

In type I, also known as postmenopausal, bone loss occurs quickly and soon after menopause. Predominantly, it is observed in the trabecular bone and is associated to vertebral and radio-distal fractures.

Type II, or senile, is related to aging and occurs due to chronic calcium deficiency, increased hormonal activity and reduction in bone formation ¹⁸.

Secondary osteoporosis is a consequence of inflammatory processes as rheumatoid arthritis, endocrine alterations as hyperthyroidism and adrenal disorders, multiple myeloma, desuse, use of drugs as heparin, alcohol, vitamin A and corticoids.

The corticoids inhibit the intestinal absorption of calcium and increase its urinary elimination, reduce the osteoblast formation and increase de osteoclastic reabsorption⁸.

Risk factors

Risks that influence the manifestation of osteoporosis are related to the people (individual) or to the environment they live (environmental).

Individual risk factors are: familial history of osteoporosis, white women, scoliosis, leanness, small constitution and premature grey hair.

Environmental factors are alcohol and tobacco (inhibitors of osteoblast multiplication), caffein (increases calcium excretion), inactivity, malnutrition, diets rich in fibers, proteins and sodium (reduce calcium absorption), nulliparity, amenorrhea due to exercise, early menopause and endocrinopathy.

DIAGNOSIS

Diagnosis is based on clinical history, physical examination and tests.

In general, osteoporosis presents few symptoms, sometimes only a fracture. Dorso-lumbar pain is a common complaint; muscular spasms are the main cause of the symptoms, also caused by microfractures; in many cases, a consequence of compression fracture.

History comprehends menopausal age, familial factors, feeding habits, physical activities, coffee intake, cigarette smoking or alcohol drinking.

Deformity of the spine is to be observed during physical examination; data about weight, height must be included aiming follow-up.

The subsidiary exams are laboratory and image testing; the former are usually normal in primary osteoporosis.

Routine blood counts, VHS, protein electrophoresis, kidney function, calcium and phosphorus determination, alkaline phosphatase and 24-hour calciuria are obtained. The endogenous calcium excretion is directly related to the onset of osteoporosis.

When necessary bone formation and reabsorption markers are also obtained.

Formation markers are bone alkaline phsphatase, osteocalcin and the pro-collagen type I C-Terminal Peptide (PICP).

Alkaline phosphatase enhances bone formation. Total alkaline phosphatase includes kidney, liver, intestine and bone phosphatases; it is the most accurate of the bone alkaline phosphatase tests.

Osteocalcin (BGP or Bone Gla Protein) gives an idea of the osteoblastic activity; pro-collagen type I C-Terminal Peptide (PICP) is the most common form of bone collagen, though it is found in other tissues.

Markers of bone reabsorption are hydroxyprolin, pyridinolin, desoxypyridinolin and Ntx.

Hydroxyprolin is a degradation product of collagen; as the main source of collagen is the bone, hydroxyprolin indicates bone reabsorption. However, it is influenced by diet.

Pyridinolin and desoxypyridinolin are measured in urine; as they are present in the collagen bonds, they are indicative of bone catabolism. They do not influence diet.

Ntx, also determined in urine, is a residue of telopeptides from the rupture of collagen type I.

There are also special exams as determination of the 25 OH vitamin D and 1.25 di OH vitamin D.

Image diagnoses comprehend X-rays and bone densitometry.

The radiographic exam shows reduction in bone density, however in a 30% range. Besides, the radiographs do not provide quantification of bone loss⁵.

X-rays reveal vertebral collapse, biconcave disk compression, Schrmol nodules and thinner corticals.

Bone densitometry is used in serial studies to quantify loss and efficiency of prevention or treatment.

The densitometry equipments are: central, to evaluate the hip, spine and body bone masses; peripherical, to evaluate fingers, wrists, patella, tibia and calcaneus bone masses.

Densitometry can be carried out using single photon, double photon (2 energy peaks), double X-rays energy (DXA), quantitative tomography and ultrasound. Among our peers DXA is the most used.

Densitometry is the best fracture predictor; the more severe the osteoporosis the greater the risk of hip fracture⁴.

TREATMENT

Prevention is the best treatment for osteoporosis; critical elements are the bone mass peak and prevention of postmenopausal reabsorption.

The bone mass peak depends on calcium and vitamin D intake, normal menstrual function, and physical activity; most of the therapeutic agents act on bone reabsorption, as anti-reabsorptives.

Calcium

Calcium intake increases with physical activity and is also higher during pregnancy and lactation. Daily need vary according to age: in adolescents, it is about 1200 mg/day; in adults, 800 mg/day; in the perimenopause, 1000 mg/day; in postmenopause, 1500 mg/day; during pregnancy reaches approximately 1500 mg/day, and during lactation, 1500 to 2000 mg/day.

The main sources of dietary calcium are milk and dairy products; however, it is also present in vegetables as spinach, water-cress, broccolli and collard green. It is often difficult to meet the calcium needs only through diet, and then supplemmentation is indicated.

The most common supplements contain calcium carbonate. They have 40% elementary calcium and solubilize in acid, so they must be administered during the meals. The presence of associated magnesium does not influence absorption, but enhances the tendency to obstipation⁸.

Supplements containing calcium citrate are indicated for subjects with achlorhydria; they reduce the risk of renal calculus⁶.

Theorically, supplementation of calcium alone can reduce fracture risks in 10%; calcium supplementation in 35 and 43 year-old women prevents bone loss and enhances bone mass at the onset of menopause¹³.

Vitamin D

UV rays act on the skin and promote the synthesis of vitamin D which undergoes transformations in the liver and kidneys to become active; it favors bone formation and eases the intestinal absorption of calcium.

In humans showing vitamin D deficiency, supplementation increases bone mass and lessens fracture risk; a 400-800 IU/day supplementation is recommended in these cases⁸.

Side effects due to vitamin D supplementation are hypercalcemia and hypercalciuria⁴.

Hormone Replacement

Estrogens

Bone loss is accelerated after menopause. Through a not very well known mechanism, the estrogens inhibit bone reabsorption and, possibly, they may act in bone formation, too.

They improve the lipidic profile, protect teeth and brain, reduce the risk of Alzheimer⁴.

Estrogen administration blocks the accelerated loss of medullary bone which occurs in the first post-menopausal years. It can reduce the incidence of spine fractures in up to 50% and of hip fractures in a lesser scale⁶.

The estrogens can be administered through oral, sublingual, transdermical, percutaneous, subcutaneous or intravaginal routes.

The dosage must be adjusted to the patient; 20% of the women who receive the conventional dosage continue to lose bone mass; women who smoke may need higher doses, obese women may need lower doses⁹.

Lane and Nydick⁸ report that a ten-year treatment with estrogens can increase in up to 43% the incidence of breast cancer. On the other hand, Tosi²⁰ states that the risk of hip fracture equals the sum of the breast, uterus and ovary cancers.

The administration of conjugated estrogens lessens the incidence of endometrial cancer related to hormones, however it does not reduce incidence as far as breast cancer is concerned.

Hormonal replacement is indicated when menopause starts and when women approach the 70s, when the risk of breast cancer is reduced and the non-skeleton effects of the treatment are noticeable. It is contraindicated when a familial tendency to breast cancer or personal history of thrombophlebitis or cerebral vascular accident are present⁸.

Selective Estrogen Receptor Modulators (SERMs)

They produce estrogenic agonism in target points as bone and liver and antagonism (or minimum agonism) in breasts and uterus. Tamoxifen and raloxifen are the most frequently used.

Tamoxifen presents about 70% of the estrogen action, considering bone mass formation⁸.

A multicentric study with 7705 postmenopausal women has shown that raloxifen reduces incidence of spine fractures but does not reduce the hip fractures incidence¹³.

Calcitonin

Calcitonin is produced by the thyroid C (parafollicular) cells. Its physiology is controverse; its ability to modulate serum calcium and phosphorus levels is significant.

Nasal sprays containing salmon calcitonin are the most frequently used therapy. It is antigenic and produces resistance when used during long periods. Its main action is to inhibit osteoclastic reabsorption; the analgesic action is significant.

Prospective studies suggest that it can reduce the incidence of spine fractures in 37%; however, the hip fractures incidence is not reduced¹⁹.

Biphosphonates

They are chemotactic to the bone surface, reduce reabsorption and increase bone formation.

Today, the most frequently used to treat osteoporosis are the alendronates.

In a random study, administration of 10 mg alendronate/day during one year produced 5% increase in the vertebra bodies bone mass and 2.3% in the femoral neck, besides providing a 47% reduction in the non-vertebral fracture incidence¹⁶.

They can cause esophagitis in up to 30% of the cases so caution is to be taken.

Endovenous pamidronate is used to treat osteolysis secondary to tumors.

Treatment of postmenopausal women with residronate showed a 41% reduction in spine fractures and up to 39% reduction in other sites¹³.

Ipriflavone

Inhibits bone reabsorption and possibly acts on bone formation.

Sodium fluoride

Enhances mineralization of the trabecular bone. Vitamin D potencializes its action in the osteoblasts.

Physical Activities

Bone mass is related to the muscular action on the bones, and gravitation exercises are more effective.

An ideal program comprehends low impact aerobic exercises, muscle strenghtening and proprioceptive improvement exercises, in order to reduce the incidence of falls¹.

Low impact aerobic exercises as walking stimulate osteoblast formation and prevent reabsorption; exercises with light weights increase muscular mass and resistance. Lower quadriceps resistance is a risk factor for hip fractures⁷.

Proprioceptive training improves walking, equilibrium and the reflexes, and prevents falls since fractures are very related to them.

Individuals who practice tai-chi-chuan have a 47% reduction in falls and ¼ reduction in hip fractures as compared to those who do not practice it¹⁷.

Swimming maintains overall relaxation and amplitude of movements more than stimulates bone production¹⁵.

The primary benefit of physical activity is to prevent bone loss resulting from inactivity, and this somehow reduces fracture risk. However, it is not recommended as a substitute for the adequate treatment with drugs.

OSTEOPOROTIC FRACTURES

Fractures and related complications are relevant clinical sequelae of osteoporosis; almost all fractures in elderly people are partially due to low bone density. Though any bone is susceptible, they occur mainly in the hip, spine, wrist and ribs.

When a fracture occurs, it is extremely important to investigate the cause. Clinical history, physical examination and laboratory exams must eliminate causes as osteomalacia, hyperparathyroidism and neoplasias.

In situations when etiological diagnosis is unknown, biopsy or anatomo-pathological sample collection must be effected in the cases with focus exposition for surgical reduction.

Low body weight, recent weight loss, previous fractures due to bone fragility, cases of osteoporotic fractures in the family and smoking are considered fracture risk factors.

Individuals with any of these factors show a greater risk for fractures, in spite of bone mass. Absence of any of these risk elements reduces fracture risk due to bone fragility. All sites prone to fractures as phalanges, vertebral bodies and long bones have the same probability to show osteoporotic fractures³.

Bone consolidation apparently is not affected in the elderly with idiopathic osteoporosis, if acceptable reduction and adequate stabilization are observed¹¹.

In general, hip fracture is a more severe condition: on average 24% of more than 50 year-old patients with hip fractures die within one year after the fracture; 25% of the patients with hip fractures demand prolonged and special care and only one third recovers entirely the independence level they had before the fracture.

Hip fractures occur 2 to 3 times more frequently in women than in men; however, mortality following hip fractures is twice in men as compared to women.

Pain, physical limitation and changes in lifestyle associated to hip and vertebrae fractures can cause psychological symptoms as depression, anxiety, fear or even rage, and hinder recovery¹⁴.

Spine fractures:

Vertebral fractures cause important complications as residual pain, reduction in height of the vertebral body and kyphosis.

Multiple toracic fractures can result in chronical pulmonary disease; fractures in the lumbar vertebrae can alter anatomy of the abdomen and cause obstipation, abdominal pain and distension, inappetence and sensation or precocious satiety.

According to Boden², 27% of the more than 65 year-old women have vertebral fractures; approximately 33% due to falls, 10 to 20% caused by raising weight, and about 50% spontaneous.

X-rays to study vertebral fractures must be taken in the anterior-posterior and profile incidences, the patient in the standing position; a tomography is indicated when reduction superior to 50% in the anterior column height or any reduction in the posterior column height of a vertebral body are observed.

When a neurological deficit is suspected, the neurological elements must be examined using tomography or magnetic ressonance; if a pathological fracture is suspected, a magnetic ressonance is effected².

Most vertebral fractures are stable so surgical stabilization is not necessary¹¹. Occasionally a temporary orthesis can be used to reduce muscular spasms and pain, but this indication above T8 is difficult. Bed rest must be avoided since it can produce a weekly loss of 1% bone mass².

Progression of deformity and pain, fractures with neurological deficit, stenosis of the vertebral canal or instability due to the fracture are indications for surgical treatment. The anterior column must always be reconstructed, when possible. There are several problems consequent to these fractures, as difficulty in fixation, risk of a fracture adjacent to the fusion, difficulty to evaluate the fusion and a number of associated clinical problems².

Kyphoplasty is a new procedure indicated in acute or sub-acute vertebral fractures caused by compression. A balloon is introduced in the fractured vertebra which is then filled with methyl methacrylate.

Lane et al.¹⁰ showed that in the first 30 patients evaluated after this procedure, there was a 45% restoration of height of the vertebral body anterior portion, 71% of the middle portion and 54% of the posterior portion; besides, 96% of the patients had quick relief of pain.

Long Bone Fractures

If the fracture is stable, with no indication for surgical treatment, long term rest must be avoided, since complications as pneumonia, congestive heart failure, thromboembolic conditions, decubitus ulcers and deterioration of muscles and bones can occur.

Immobilization with a plaster must be very well cushioned due to the bad quality of the elderly skin, particularly when neuropathy or vascular conditions are present.

Most fractures of the long bones are better treated with early surgical stabilization providing quick support for the lower limbs or functional recovery of the upper limbs¹¹.

FINAL CONSIDERATIONS

Osteoporosis reflects inadequate accumulation of bone mass during growth and maturity, excessive loss or both. As no effective way exists to reconstruct the skeleton, prevention is the primordial strategy.

As fractures in general occur after falls, shoes with rubber soles should be used; a walking stick provides support and improves walking stability; care must be taken with slippery floors and shoes; walking using only socks must be avoided; supporting bars and rubber floors in the bathroom; small guiding lights to help locomotion during the night; avoid carpets and other objects which can provoke stumbling; improve sight condition.

At any age, avoid tobacco; alcohol and coffee intake must be moderate; physical activity and adequate amounts of calcium are fundamental.

In peri- and postmenopause, when a familial history of osteoporosis is present, bone densitometry must be yearly controlled. Eventually, hormonal replacement should be instituted and supplementation with calcium and vitamin D is important for the elderly.

REFERENCES

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• 3. Cummings, S.R. , Nevitt, M.C. , Browner, W.S. et al : Risk factors for hip fracture in white women. N Engl J Med 332 : 767-773, 1995.
• 4. Einhorn, T.A. : Osteoporosis in orthopaedic practice American Academy of Orthopaedic Surgeons 65^th Annual Meeting, New Orleans, 1998.
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• 10. Lane, J.M. , Girardi, F. , Parvataneni, H. et al : Preliminary outcomes of the first 226 consecutive kyphoplasties for the fixation of painful osteoporotic vertebral compression fractures World Congress on Osteoporosis 2000, Chicago, 2000.
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• ¹⁴
  National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis Washington D.C. , 1998.
• 15. Plapler, P. : Osteoporose e exercícios. Acta Ortop Bras 4 : 43-46, 1996.
• 16. Pols, H.A.P. , Felsenberg, D. , Hanley, D.A. et al : Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: Results of the FOSIT study. Osteoporos Int 9 : 461-468, 1999.
• 17. Province, M.A. , Hadley E.C. , Hornbrook, M.C. et al : The effects of exercise on falls in elderly patients. A preplanned meta-analysis of the FICSIT Trials. JAMA 273 : 1341-1347, 1995
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• 19. Silverman, S.L. , Chesnut, C. , Andriano, K. et al : Salmon calcitonin nasal spray (NS-CT) reduces risk of vertebral fracture(s) in established osteoporosis and has continous efficacy with prolonged treatment : Accrued 5 year worldwide data of the PROOF Study. Bone 23, suppl. 5 : S 174, 1998.
• 20. Tosi, L.L. : Diagnosis and managment of orthopaedic problems commonly found in women : osteoporosis American Academy of Orthopaedic Surgeons 65^th Annual Meeting, New Orleans, 1998.
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Publication Dates

• Publication in this collection
  17 May 2006
• Date of issue
  June 2001