The American College of Physicians (ACP) published an updated 2023 guideline on drug therapy for patients with reduced bone density or osteoporosis. An extensive secondary analysis published last year has been incorporated as the evidence base. A bottom line of the new ACP guidelines is that the place of bisphosphonates as first-line therapy has been strengthened.
Primary osteoporosis is characterized by a loss of bone mass and density leading to an increased risk of fracture, particularly of the hip and spine [1]. According to the WHO classification, a T-score of -1.0 to -2.5 is osteopenia and -2.50 or below is osteoporosis [2]. The T-score represents the standard deviation of bone density compared to 20-29 year old individuals of the same sex. Fractures can occur in any part of the body, but hip and spine fractures account for 42% of all osteoporotic fractures [3]. The 2023 secondary analysis by Ayers et al. published in the Annals of Internal Medicine. on which the updated American College of Physicians (ACP) recommendations for the treatment of osteoporosis are based, included 34 randomized controlled trials (RCTs) and 36 observational studies [3,4].
Value of bisphosphonates as first-line therapy underpinned
The new ACP guidelines recommend bisphosphonates as first-line therapy for postmenopausal women and for men with primary osteoporosis-with the exception of women at very high risk of fracture [3,4]. In this group, the osteoanabolic substances romosozumab (sclerostin inhibitor) or teriparatide (recombinant parathyroid hormone) can be used initially for 1 or 2 years, respectively, followed by bisphosphonate therapy to prevent renewed bone mass loss. The use of denosumab is advocated as second-line therapy for men and women with contraindications (or side effects) to bisphosphonates. Similar to the 2017 guideline version, the ACP suggests prescribing bisphosphonates in women over 65 years of age with low bone mass/osteopenia, depending on their risk profile, as part of an individualized treatment approach.
Treatment effects in postmenopausal women with osteoporosis.
Most of the 34 RCTs and 36 observational studies that served as the evidence base for the ACP guidelines in the secondary analysis included data on postmenopausal women with osteoporosis [4]. The following are the main results for this patient population (Table 1, Table 2) .
Risk of hip fracture: Compared with placebo, bisphosphonates reduced the risk of hip fracture by 65% over a 24-month period and by 64% over a 36-48-month period. Denosumab therapy for 36 months reduced hip fracture risk by 61%. In women at very high risk of fracture based on age and history, sequential treatment with romosozumab followed by alendronate proved more effective in reducing hip fracture risk than alendronate alone with respect to a 24-month period (RR 0.62; CI 0.42-0.91].
Clinical spine fractures: treatment with bisphosphonates for 12 to 36 months and 36 months of denosumab therapy reduced the risk of clinical spine fractures by 54-68% compared with placebo. Teriparatide was associated with a 76% risk reduction at 17 months, and romosozumab reduced risk by 82% at 12 months. The only treatment option that proved more effective than bisphosphonates in reducing the risk of clinical spine fractures was sequential treatment with romosozumab followed by alendronate for 24 months.
Other fractures: Over a period of 12 to 36 months, all treatment options except denosumab showed a reduction in the risk of other clinical fractures in the placebo comparison. With respect to 36 months or more, bisphosphonates and denosumab reduced the risk of clinical fractures, but bazedoxifene and raloxifene did not. In women at very high risk of fracture, sequential treatment with romosozumab followed by alendronate proved more effective than alendronate alone (RR 0.74; CI 0.63-0.89), and teriparatide showed greater efficacy than risedronate at 24 months (RR 0.64; CI 0.43-0.95]. Regarding abaloparatide (18 months; RR 0.35 [KI 0,15–0,81]) and raloxifene (12 months; RR 0.17 [KI 0,03–0,81]), there were moderate effects. In a 19-month head-to-head RCT, abaloparatide was found to be more effective in reducing clinical fractures compared with teriparatide (RR 0.43 [KI 0,21–0,90].
Congress: Practice Update
Literature:
- Fassnacht M: Thyroid gland. Endocrinology, Manual, Practice Update, Berlin, April 28-29, 2023.
- Kanis JA; on behalf of the World Health Organization Scientific Group. Assessment of osteoporosis at the primary health-care level. Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield; 2007. Accessed at www.sheffield.ac.uk/FRAX/pdfs/WHO_Technical_Report.pdf on 20 July 2022, (last accessed 10 Jun 2023).
- Qaseem A., et al: Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians. Ann Intern Med 2023; 176(2): 224-238.
- Ayers C, et al: Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Metaanalysis for the American College of Physicians. Ann Intern Med 2023; 176(2): 182-195.
HAUSARZT PRAXIS 2023; 18(6): 22–23
