postmenopausal osteoporosis.
In November of 2023 two New York Professors reviewed our approach to postmenopausal osteoporosis. Much of this summary comes directly from their article in the New England Journal of Medicine—November 23, 2023.
Much as the steel beams of a building provide a scaffold to support its weight, the bones and cartilage of our skeletal system compose the scaffold that supports the rest of the body. Throughout our lives our skeleton is continuous remodeling itself. Cells called osteoclasts remove minerals and cells called osteoblasts form a new bone. It’s believed that 1 million BRUs (bone remodeling units) are actively engaged in bone turnover at any time, 3–4 million bone remodeling units (BRUs) are initiated each year, and the adult skeleton is renovated every 10 years.
The remodeling process adjusts bone architecture to meet changing mechanical needs and it helps to repair damaged bone. After a person’s is fully grown and the skeleton has attained peak bone mass, bone remodeling is balanced and our bone mass is stable for a decade or two. Then age-related bone loss begins. Our resorptive activity exceeds new bone formation and bones are weaker.
Postmenopausal osteoporosis is caused by estrogen deficiency. It leads to an increase in osteoclast differentiation and activation. Bone resorption outpaces formation, and rapid bone loss occurs, particularly in the years immediately before and after menopause. As bone mineral density and bone strength decrease, the risk of fragility fractures increases. Postmenopausal osteoporosis is diagnosed on the basis of the occurrence of a fragility fracture (with no associated trauma or with trauma equivalent to falling from a standing height or less) or bone mineral density at the spine, total hip, or femoral neck that is at least 2.5 standard deviations below the mean of that in a young adult reference population (T score of −2.5 or less), as measured with the use of DXA. dual-energy x-ray absorptiometry scan.
Osteoporosis is asymptomatic until the first clinical fracture and the DXA is the gold standard for measuring bone mineral density and identifying patients at risk. Each standard deviation reduction below a T score of 0 is associated with a doubling or tripling in the risk of fracture.
In the United States, approximately 20% of women over 50 years of age and 30% of women 65 years of age or older meet DXA criteria for osteoporosis. In the United States, osteoporosis is more common among White, Asian, and Hispanic women than among non-Hispanic Black women. An additional 40% of postmenopausal women have low bone mass (osteopenia; defined as a T score between −1.0 and −2.49). Approximately 50% of postmenopausal women will have fragility fractures, which cause pain, disability, and decreased quality of life. After a hip fracture, many women never regain independence, 20% are institutionalized, and the risk of death within 1 year doubles. Non-White women who have hip fractures are more likely to die within 6 months, are less likely to regain independence, and have less timely surgery and rehabilitation than White women who have hip fractures.The annual health care cost associated with fractures related to postmenopausal osteoporosis in the United States, currently $57 billion, is projected to exceed $95 billion by 2040.
By 75 years of age, approximately half of the population will have osteoporosis. Vertebral compression fractures, the most common osteoporotic fractures, are frequently painful and cause height loss but may be asymptomatic. In addition, there is an increased risk of falling which increases the risk of fracture; one in two women and one in five men over the age of 50 in the UK will fracture a bone, mainly as a result of skeletal fragility.
The most common fractures in people with osteoporosis are of the wrists, hips and spinal bones; these are most common in older people, but younger people can sometimes be affected.
Patients should be encouraged to stop smoking, avoid excessive alcohol, increase weight-bearing exercise, and prevent falls. Most guidelines recommend 1000 to 1200 mg of calcium daily in women with postmenopausal osteoporosis, preferably obtained from diet, and 400 to 1000 IU of vitamin D daily.
All pharmacologic approaches reduce vertebral fracture risk, and some reduce the risk of non-vertebral and hip fractures. Most guidelines recommend bisphosphonates as initial treatment, given their efficacy, safety, convenience, low cost, and enduring effects after discontinuation. Four oral and intravenous bisphosphonates are FDA-approved for postmenopausal osteoporosis. All reduce the risk of vertebral fracture. All but ibandronate reduce the risk of hip and non-vertebral fractures.
Long-term use of bisphosphonates has been associated with osteonecrosis of the jaw and atypical femur fractures. Osteonecrosis of the jaw is an area of exposed jaw bone that does not heal within 8 weeks after identification by a health care provider. Atypical femur fractures are low-trauma subtrochanteric or femoral-shaft fractures with specific radiographic criteria. In patients receiving bisphosphonates at doses used for postmenopausal osteoporosis, the estimated risks of osteonecrosis of the jaw and atypical femur fracture are very low.
Denosumab
In randomized, controlled trials conducted over a period of 3 years, denosumab lowered the risk of spine, hip, and non-vertebral fractures as compared with placebo. In long-term, open-label extension studies, the lower risk of fractures was maintained. Although gains in bone mineral density are greater with denosumab than with bisphosphonates, evidence for greater reduction of fracture risk is limited. Denosumab is also rarely associated with osteonecrosis of the jaw and atypical femur fracture. After denosumab therapy is discontinued bone resorption and rapid bone loss is accelerated. The incidence of multiple vertebral fractures was higher after discontinuing denosumab than after discontinuing placebo (3.4% vs. 2.2%) Weekly administration of alendronate, initiated 6 months after receipt of the last dose of denosumab, may prevent bone loss.
Parathyroid hormone (PTH) receptor agonists include teriparatide (PTH 1-34) and abaloparatide (PTHrP 1-34). As compared with placebo, treatment for 18 to 24 months with teriparatide or abaloparatide reduces vertebral and nonvertebral fracture risk. Neither drug has been shown to reduce the incidence of hip fractures, but studies were underpowered for this outcome. Both agonists require daily injections.
Romosozumab, given monthly as subcutaneous injections, is the newest FDA-approved therapeutic for postmenopausal osteoporosis. In a phase 2 study, romosozumab increased bone mineral density more than teriparatide. In the Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), Romosozumab reduced the risk of vertebral and clinical (composite symptomatic vertebral and nonvertebral) fractures at 12 months as compared with placebo. The risk of vertebral fracture remained lower in the romosozumab group after 1 year of treatment with denosumab—however the drug led to a higher incidence of serious cardiovascular events (2.5% vs. 1.9%) and that led to an FDA black-box that warned against the use of romosozumab within 1 year after myocardial infarction or stroke.
https://www.nejm.org/doi/full/10.1056/NEJMcp2307353?query=featured_home
Comments
Post a Comment