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Osteoporosis in the oldest of the old: to treat or not to treat?

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Women are at greater risk of osteoporosis due to the fact that they reach a lower peak bone mineral density (BMD) compared to men, as well as a decline in oestrogen post-menopause. An estimated 200 million women are affected. The risk of osteoporosis increases with age and it is estimated that >60% of women aged 90 have osteoporosis.

Women are also at greater risk of fracture. About 80% of forearm fractures, 75% of humerus fractures, 70% of hip fractures, and 58% of spine fractures occur in women.

Fractures are a leading cause of morbidity and mortality

Hip fractures cause the most morbidity and mortality rates of between 20%–24% in the first year after a hip fracture have been reported. Patients who sustain hip fracture, die within the first three to six months following the event. According to the World Health Organization (WHO) fractures account for about 1% of the disability-adjusted life year attributable to non-communicable diseases.

The WHO stresses that because of the morbid consequences of osteoporosis, the prevention of this disease and its associated fractures are essential to the maintenance of health, quality of life (QoL), and independence in the elderly population. Within one year after a hip fracture, 40% of patients were unable to walk independently, 33% of them were dependent or in a nursing home.

Management challenges

Octo- and nonagenarians bear the greatest burden of osteoporosis related fractures and consequent morbidity and mortality. But despite this, osteoporosis continues to be underdiagnosed and undertreated in old age – even in those hospitalised with documented fractures, state Vandenbroucke et al.

According to Masud there is enough evidence to suggest that the oldest old should be considered for osteoporosis treatment as well having a focus on falls reduction.

Vandenbroucke et al conducted an in-depth analysis of the available osteoporosis pharmacotherapies available. The team concluded that large pivotal fracture trials have shown that, in general, osteoporosis treatment in elderly and very elderly patients is well tolerated, with adverse events that tend to be mild to moderate, with no significant differences in the incidence of most adverse events in the treated group compared with the placebo group. Overall, the incidence of adverse events in the very elderly was similar to that reported in the general population. However, in real life, specific issues such as comorbidity and polypharmacy should be considered in the very elderly and may influence the choice of therapy.

Rizzoli et al found that drug-drug interactions are rare. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment.

Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both exceedingly rare). The selective oestrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both exceedingly rare) and teriparatide with headache, nausea, dizziness, and limb pain.

In another study, Rizzoli et al concluded that people >80-years of age stand to gain substantially from effective anti-osteoporosis treatment, but the under-prescription of these treatments is frequent.

Guideline recommendations

However, in 2020 The International Conference on Frailty and Sarcopenia Research Task Force published guidelines for the treatment of osteoporosis in frail, older adults. According to Rolland et al, agree that after diagnosis, treatment for osteoporosis is not routinely given to older adults. Furthermore, as a result of for example cognitive impairment, adherence to medical regimens is poor.

The task team recommended the following:

Traditional care system is inadequate for dealing with complex health disorders of ageing such as frailty and cognitive impairment. Furthermore, although the pathophysiology of bone fracture is the same in frail and non-frail adults, the mechanisms (eg poor balance, sarcopenia, poor physical performance, sedentary lifestyle, and poor nutritional status) that lead to bone fracture poor - differ. Therefore, a multidisciplinary approach and comprehensive interventions (eg nutritional and exercise) are required to manage these patients

Reducing fracture risk among older adults requires first intervening with a powerful agent to restore the strength of bone, and then switching to an anti-resorptive agent to maintain bone health. The high cost of many of these drugs imposes a barrier but fractures themselves are costly and health economics studies show that bone forming agents are cost-effective even over short time periods. Combination therapies are also recommended, not just for treating the bone but for other factors as well, particularly in individuals who are frail.

Frail, older adults often take many drugs due to comorbidities, raising questions about the value of further adding drugs to treat osteoporosis versus decreasing drug consumption in frail older adults. Targeted therapies can reduce the need for polypharmacy.

REFERENCES:
  • Berry SD, et al. Considering the Risks and Benefits of Osteoporosis Treatment in Older Adults. JAMA Intern Med. 2019
  • Tan, LF, Ying SM, Teng J et al. The Impact of Frailty, Falls and Cognition on Osteoporosis Management in the Oldest Old. Calcif Tissue Int, 2022.
  • De Villiers TJ and Goldstein SR. Bone health 2022: an update. Climacteric, 2022.
  • WHO. Assessment of osteoporosis at the primary health care level. https://www.sheffield.ac.uk/FRAX/pdfs/WHO_Technical_Report.pdf
  • Vandenbroucke A, et al. Pharmacological treatment of osteoporosis in the oldest old. Clin Interv Aging, 2017.
  • Barnsley, et al. Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people. Aging Clin Exp, 2021.
  • Masud T. Evidence Base for Treatment of Osteoporosis in Older People. Age and Ageing, 2019.
  • Felsenberg D, et al. Placebo-controlled multicenter study of oral alendronate in postmenopausal osteoporotic women. FOSIT-Study-Group. Fosamax International Trial. Maturitas, 1998.
  • McClung MR, et al. Effect of Risedronate on the Risk of Hip Fracture in Elderly Women. NEJM, 2001.
  • Vondracek SF and Linnebur SA. Diagnosis and management of osteoporosis in the older senior. Clin Interv Aging, 2009.
  • Black DM, et al. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. NEJM, 2007.
  • Cummings SR, et al. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. NEJM, 2009.
  • Neer RM, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med, 2001.
  • Boonen S, et al. Safety and efficacy of teriparatide in elderly women with established osteoporosis: bone anabolic therapy from a geriatric perspective. J Am Geriatr Soc, 2006.
  • Rizzoli R, et al. Adverse reactions, and drug-drug interactions in the management of women with postmenopausal osteoporosis. Calcif Tissue Int, 2011.
  • Rizzoli R, et al. Management of osteoporosis of the oldest old. Osteoporosis, 2014.
  • Rolland Y, et al. Osteoporosis in frail older adults: recommendations for research from the ICFSR Task Force 2020. J Frailty Aging, 2021.

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