Osteoporosis
From Standard of Care
Characterized by decreased trabecular or cortical bone volume.
Affects up to 30% of women and 12% of men during lifetime.
Affects 4-6 million women and 1 million men in the U.S.
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.
Elderly women of European descent at highest risk.
Increase in frequency with advanced age and account for 95% of hip fractures in the elderly.
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.
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.
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. 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.
Most patients at significant risk for fractures do not receive adequate preventive treatment.
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, and multiple myeloma.
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.
