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Osteoporosis

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Characterized by decreased trabecular or cortical bone volume.

Age-related change in bone mass occurs when there is an imbalance in bone formation and bone resorption. 

 

 

With osteoporosis there is decreased bone formation with decreased osteoblastic activity and increased bone resorption by osteoclastic activity.

Osteoporosis is typified by low bone mineral density (BMD), reduced bone mass, microarchitectural deterioration of bone and increased bone fragility.

 

With osteoporosis  increased osteoclastic activity is significantly exacerbated by estrogen loss, especially during menopause in women.

Osteoporosis is defined by the World Health Organization in women as a bone mineral density 2.5 standard deviations below peak bone mass, relative to the age and sex-matched average, as measured by Dual energy X-ray absorptiometry

Most common in women after menopause, when it is called “postmenopausal osteoporosis”, but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids.

Usually has no symptoms until a fracture occurs.

Affects up to 30% of women and 12% of men during lifetime.

A key predisposing factor for fragility type fractures that occur with minimal or low impact trauma.

Affects 4-6 million women and 1 million men in the U.S.

Approximately 9,000,000 osteoporotic fracture’s per year occur globally, most of which are observed in postmenopausal women.

Lifetime risk of osteoporotic fracture is estimated to be 13-22% in men 50 years and older.

Due to a higher peak bone mass and no substantial loss in estrogen men are likely to develop osteoporosis approximately 10 years after women. 

Strongly associated with aging, affecting at least 10-25% of men who are 60 years older.

Lifetime risk of osteoporotic fracture for a 50-year-old Caucasian women estimated to be 30-40%, including a 15% -18% lifetime risk for hip fracture.

Hip fracture is the most devastating complication of osteoporosis, especially for the elderly.

Elderly women of European descent at highest risk.

Increase in frequency with advanced age and account for 95% of hip fractures in the elderly.

While the prevalence of osteoporosis is more common among some populations:white women, persons with low body mass), osteoporosis is seen in all racial and ethnic groups, all weight categories, and in both men and women. 

Following an initial fracture osteoporosis screening should occur due to an increase risk of future fractures , including the 2ofold greater risk for clinically serious hip or spine fractures.

A skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture.

Fractures that occur with minimal trauma, fragility fractures, are the hallmark.

Vertebral fractures are the most common osteoporotic fractures.

Low bone mass and microarchitectural deterioration of bone tissue that may lead to increased bone fragility and fracture risk.

In most postmenopausal women bone loss from trabecular sites averages about 1% per year.

In men a major cause is hypogonadism.

Almost 20% of men at least 50 years of age have osteoporosis of the hip, spine, or wrist.

Prevalence of hip or vertebral fractures in older man is approximately one third that in age-matched women.

Many men in this age group have a 13% lifetime risk of an osteoporotic fracture.

For residents in nursing facilities, the prevalence of osteoporosis exceeds 50% regardless of race or gender.

Astronauts lose between 1-2% of their bone mass per month due to zero gravity in space.

Adjuvant chemotherapy-induced ovarian failure cause rapid and significant bone loss.

Estimated 15% of premenopausal women have a bone mineral density lower than 1.0 SD below the young-adult mean and 0.6% have a BMD lower than 2.5 SD below that mean.

Fractures, especially of the hip, highest in white women.

Most common metabolic bone disease cause greater than 1.3 million fractures per year including 250, 000 hip fractures.

Early menopausal bone loss from the lumbar spine and femoral neck is attenuated in long-term users of depot medroxyprogesterone.

30% of all postmenopausal women eventually sustain such fractures.

80% of patients are not diagnosed.

Salmon calcitonin nasal spray significantly reduces the risk of new vertebral fractures in postmenopausal women.

5% of patients with LHRH antagonists develop osteoporotic fractures.

Risk for fracture in patients with inflammatory bowel disease is increased by 40%.

Approximately 1.5 million men have osteoporosis.

Hypogonadism an important cause of osteoporosis and fractures in men.

Associated with the presence of cataracts, with pathophysiological associations with both conditions, such as calcium imbalance, hormonal abnormalities, and shared genetic predisposition.

Androgen deprivation, the mainstay of treatment for prostate cancer decreases mineral density by 4-13% per year and increases fracture rate.

Obesity is a negative risk factor.

Bone density increases with the number of deliveries until the age of 69 years.

Regular physical exercise can reduce the risk and delay the decrease of bone mineral density.

Medications for the treatment or prevention of osteoporosis falls into two categories: one anti-resorptive drugs or formation stimulating drugs.

Anti-resorptive drugs include bisphosphonates, a selective estrogen receptor modulator, estrogen, calcitonin and a monoclonal antibody against receptor activator of nuclear factor-kB ligand.

The US Preventative Services Task Force recommends against using supplements of vitamin D and calcium to prevent fractures: in the review of six randomized trials there was no evidence of benefit from taking 400 international units of vitamin d3 and 1000 mg of calcium daily, but one in every 273 women who took supplements for at least seven years developed kidney stones.

Daily dietary recommendations are intake of calcium to be 1,500 mg/day for men and women aged 65 and older. 

 

 

Preferably, calcium intake should be in the form of dairy products to improve absorption. 

 

Calcium carbonate and calcium citrate may be used as dietary supplements. 

 

Additionally, calcium should be taken in divided doses to improve absorption.

The only formation stimulating agent presently is teriparatide.

Parathyroid hormone and bisphosphonates increase bone density as monotherapy but the increase in central bone mass is less than use of parathyroid hormone alone.

Secondary type most frequently related to exogenous steroid therapy.

Secondary causes of osteoporosis include low body weight with a body mass index of less than 20 kg/m2, use of systemic glucocorticoid therapy for 3 or more months, family history of osteoporotic fracture, early menopause, current smoking status, and excessive consumption of alcohol.

Most patients at significant risk for fractures do not receive adequate preventive treatment.

Recommendations for treating osteoporosis:

 

 

Pharmacological treatment is instituted in those with BMD T-scores worse than −2.5, or worse than −2.0 and multiple risk factors.

 

 

For those with a history of vertebral or hip fracture. 

 

 

Treating osteoporosis and osteopenia should begin with appropriate supplementation of calcium and vitamin D. 

 

Calcium has been shown to increase BMD when administered with vitamin D and it is co-administered with most therapeutic agents for osteoporosis.

 

Following solid organ transplantation there is a significantly high risk of osteoporosis and bone fracture during long-term follow-up:pre-existing underlying diseases and immunosuppressive therapy for important factors in the development of bone disease in such patients.

A T score for bone mineral density is below-2.5.

While treatment may decrease risk of fracture by as much as 50% women may still have fractures.

A substantial number of women with T scores above -2.5 sustain fractures.

In some instances spine and hip T scores may have substantial discrepancy.

Secondary causes include hyperparathyroidism, vitamin D deficiency due to low intake, lack of exposure to sunlight, malabsorption syndromes, multiple myeloma, celiac disease, Cushing’s disease, hypothyroidism, hypogonadism, neuromuscular diseases such as cerebral palsy, malnutrition, and, lead exposure.

Medications associated with adverse skeletal effects include: glucocorticoids, unfractionated heparin, aromatase inhibitors, gonadotropin releasing hormone agonists, medroxyprogesterone acetate, and excessive thyroid hormone, thiazolidinedions, proton pump inhibitors, serotonin selective reuptake inhibitors, anti-epileptics and calcineurin inhibitors.

Glucocorticoids decrease bone formation by indirect effects on osteoblasts, and increased osteocyte apoptosis and initially increase the lifespan of mature osteoclasts.

Glucocorticoids have secondary effects that are damaging to the skeleton and include decreased intestinal calcium absorption, increased urinary calcium excretion, hypogonadism, and muscle weakness.

Glucocorticoids increase the risk of fracture, especially of cancellous bone such as a vertebrae.

The goal of treatment is to reduce risk of clinical fracture.

Drug therapy should be initiated in post menopausal women with osteoporosis manifested by a hip or spine bone mineral density (BMD) T score less than or equal to -2.5 or personal history of fragility fracture of the hip or vertebrae.

 

Pharmacologic therapy is strongly recommended for patients who have:

 

 

A T-score of -2.5 or lower in the spine, femoral neck, total hip.

 

 

Osteopenia or low bone mass and a history of fragility fracture of the hip or spine.

 

 

A T-score between -1.0 and -2.5 if the FRAX® 10-year probability of a major osteoporosis-related fracture is 20% or higher or the 10-year probability of hip fracture is more than 3% in the United States

 

 

 

Approved agents with efficacy to reduce hip, nonvertebral, and spine fractures, include:

 

 

 alendronate, risedronate, zolendronate, and denosumab.

 

 

Abaloparatide, denosumab, romosozumab, teriparatide, and zoledronate should be considered for patients unable to use oral therapy and as initial therapy for patients at very high risk of fracture. 

 

 

Ibandronate or raloxifene may be appropriate initial therapy in some cases for patients requiring drugs with spine-specific efficacy.

 

 

Comparing baseline DEXA scans to follow-up scans for 1 to 2 years are recommended.

 

 

Scans be done at the same facility and with the same DEXA machine to avoid any machine mishaps. 

 

 

Successful treatment of osteoporosis is stable to increasing bone mineral density with no evidence of new fractures or vertebral fracture progression. 

 

 

Bone turnover markers and bone formation markers are used for benchmark progress and to measure treatment success. 

 

 

For abaloparatide and teriparatide, use can last up to 2 years, followed by a bisphosphonate or denosumab. 

 

 

Romosozumab can be taken up to 1 year, followed by a bisphosphonate or denosumab. 

 

 

Oral bisphosphonate can be taken up to 5 years if the fracture risk is no longer high or 6 to 10 years if fracture risk persists. 

 

 

Zolendronate can be taken up to 3 years in high-risk patients or until fracture risk is no longer high and up to 6 years in very high-risk patients.

Some recommend initiation of treatment in postmenopausal women with osteopenia with BMD T score between -2.5 and -1.0 who have a 10 year fracture probability at or above interventions thresholds, but the benefit of treatment in such patients has not been assessed in clinical trials.

World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Disease (WCO-IOF-ESCEO) 2020 virtual congress, study results indicate hormone therapy with estrogen or estrogen plus progestin was associated with a 28% reduction in all fractures and a 34% reduction in osteoporotic fractures over an 8-year follow-up period.

Treatment with Alendronate, risedronate, and zoledronate lowers risk of vertebral and nonvertebral fractures including hip fractures.: The differences in effectiveness between these three bisphoshanates likely to be small.

There is no evidence for ibandronate reducing risk of non-vertebral fractures.

Routine laboratory tests for the evaluation of osteoporosis should include a serum calcium, 25-hydroxy vitamin D, a complete blood count, and 24-hour urinary calcium excretion. Elevated calcium suggests hyperparathyroidism and decreased calcium suggests malabsorption or vitamin D deficiency/resistance. 

 

 

Anemia may indicate multiple myeloma. 

 

Additional laboratory tests such as parathyroid hormone, thyroid-stimulating hormone, and serum protein electrophoresis may be indicated after the initial evaluation.

Osteopetrosis is a heterogeneous group of heritable disorders with defective osteoclast mediated bone resorption.

A clinical syndrome characterized by the failure of osteoclasts to resorb bone.

Associated with impaired bone modeling and remodeling.

The defect in bone turnover results in skeletal fragility, increased bone mass, and it may also cause hematopoietic insufficiency, disturbed tooth eruption, nerve entrapment syndromes, and growth impairment.

A heterogeneous disorder encompassing different molecular lesions and a range of clinical features.

All types of lesions share abnormalities in the osteoclast.

3 distinct clinical forms of the disease—infantile, intermediate, and adult are diagnosed in infancy, childhood, or adulthood, respectively, account for most cases.

Often diagnosed incidentally and before age 1y ear.

A rare form of osteopetrosis occurs in association with renal tubular acidosis and cerebral calcification due to carbonic anhydrase isoenzyme II deficiency.

Incidence is estimated to be 1 case per 100,000-500,000 population. How

In infantile osteopetrosis, bone marrow failure may occur, leading to death by the first decade of life.

Infantile disease associated with failure to thrive, have growth retardation, and other disabilities.

Some patients with infantile osteopetrosis can undergo bone marrow transplantation (BMT).

Patients with adult form of osteopetrosis have good long-term survival rates.

 

 

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