According to guideline recommendations, individualized long-term measures must be adapted to the personal risk profile and disease activity. The overriding treatment goal is the best possible reduction of future fracture risk. To achieve this, meaningful sequential therapy is the most promising approach. This allows a sustainable long-lasting effectiveness to be achieved.
Osteoporosis and the associated increased risk of fractures is a significant health problem in the aging population. Bone mass loss and deterioration of bone structure increase the risk of fractures, which can lead to loss of mobility and quality of life. In Switzerland, osteoporosis ranks sixth on the list of the most common chronic diseases with 6% [1].
According to epidemiological data, the prevalence is most common in the age group over 65 years. Women are more than twice as likely to be affected as men, mainly due to hormonal changes after menopause. In Switzerland, for example, a 50-year-old woman has a 51.3% risk of sustaining one of the four most common osteoporosis-related fractures (hip region, vertebral body, radius, or femur) during the rest of her life.
In contrast, for men, the corresponding lifetime risk is 20.2% [1]. As a result of a fracture, there may be fear of movement and associated loss of mobility. Lack of exercise in turn increases the risk of a new fracture. Nowadays, risk-adapted and effective management of osteoporosis can be achieved through individualized long-term strategies, said Prof. Franz Jakob, MD, of the Musculoskeletal Center Würzburg (D), at this year’s DGIM Annual Meeting. The earlier osteoporosis is detected, the better the opportunities for effective risk-adapted treatment (Fig. 1) 2 ].
FRAX score for multifactorial risk assessment
The 2020 updated recommendations of the Swiss Osteoporosis Association (SVGO) define criteria for risk stratification and therapy recommendations based on these criteria [3]. The diagnosis of osteoporosis is based on a comprehensive risk assessment, and fracture risk is not solely dependent on bone density, but also on many other risk factors. A multifactorial risk assessment is possible, for example, with the “WHO Fracture Risk Assessment Tool” (FRAX) [4]. The FRAX score is a validated tool applicable in men and women over 45 years of age to estimate the 10-year risk of major fractures of the hip, spine, forearm, or proximal humerus [4,5]. In addition to age and gender, other risk factors such as BMI <20, a fracture after the age of 40 (excluding hands, feet, skull) and a fracture of the neck of femur in one of the parents are taken into account. Also contributing to an increased risk are the presence of rheumatoid arthritis or current or previous oral glucocorticoid therapy for a period of at least 3 months daily (≥5 mg prednisolone equivalent).
Adapt treatment strategy to individual fracture risk
Bone densitometry is used to confirm the diagnosis of osteoporosis. In postmeopausal women, estrogen deficiency is by far the most likely cause of osteoporosis or increased fracture risk. However, other possible causes should still be excluded by differential diagnosis. The current SVGO recommendations distinguish risk categories, for each of which a specific treatment algorithm is proposed (Tab. 1). The implementation of basic measures is recommended for each of the risk groups (sufficient intake of calcium, vitamin D and proteins, regular physical activity, prevention of falls, avoidance of nicotine, low alcohol consumption, avoidance of medications with unfavorable influence on bone metabolism). [3,6]. The drug treatment options for osteoporosis can be divided into two categories: antiresorptive procedures, i.e., procedures that protect against bone loss, and bone-building procedures. Antiresorptive drugs include bisphosphonates, which are incorporated into the bone and taken up by the osteoclasts that break down bone, inhibiting their function. Regular progress controls are very important. Bone densitometry/DXA should be performed every 2 years, except in low-risk patients in whom DXA at 5-10 year intervals is sufficient.
Individualized sequence therapy most promising
Long-term therapy consists of reasonable sequences; lifelong therapy with a single drug is not currently feasible. Like bisphosphonates, the RANKL antibody denosumab (Prolia®) has an antiresorptive effect. The mechanism of action of the monoclonal antibody is that it targets the “Receptor activator of NF-κB ligand” (RANKL), a key factor in the development of osteoclasts. Bone-building methods include teriparatide, a fragment of human parathyroid hormone. For patients, professional use of these modern osteoporosis therapeutics offers a permanent, safe and effective risk reduction of fractures.
Denosumab clinically results in rapid inhibition of bone resorption rate, increase in bone density, and decreased fracture incidence predominantly of vertebral fractures in postmenopausal women. In the FREEDOM trial of 7868 postmenopausal women, treatment with denosumab over a three-year period significantly reduced the relative risk of new fractures in the vertebrae by 68%, in the hip by 40%, and in nonvertebral fractures by 20% [7,8]. This is a significantly higher risk reduction than can be achieved with bisphosphonates. Another advantage of denosumab is that it must be applied subcutaneously every six months. In contrast, bisphosphonates require much more frequent application.
In particular, patients with initially severely reduced bone density may benefit from denosumab. “Rebound” effects, i.e. rapid restimulation of bone resorption with subsequent increased vertebral fracture risk after discontinuation of denosumab, can be counteracted by adequate follow-up therapy. According to one study, the parenteral bisphosphonate zoledronate, as a single intravenous injection six months after the last dose of denosumab, can prevent reactivation of bone resorption for another two years [9]. After discontinuation of Prolia® , recommends the use of bisphosphonates [10] for follow-up treatment. According to the current state of knowledge, rebound can be most efficiently counteracted by zoledronate i.v. 5 mg 1× per year, first administration 6 months after the last Prolia® application; alternatively, aledronate can be used [9]. Bone remodeling markers should be measured every three to six months to monitor follow-up [10]. Direct switching from Prolia® to osteoanabolic therapy such as teriparatide should be avoided. A combination of biphosphonates and Prolia® [11] is also not recommended.
Literature:
- Rheumaliga Schweiz: Strategy Musculoskeletal Diseases, www.rheumaliga.ch/assets/doc/CH_Dokumente/blog/2017/strategie/Nationale-Strategie-Muskuloskelettale-Erkrankungen-Langfassung.pdf (last accessed 16.03.2021).
- Jakob F: Update Osteoporosis, Prof. Dr. Franz Jakob, DGIM Annual Meeting, 19.04.2021.
- Ferrari S, et al: 2020 recommendations for osteoporosis treatment according to fracture risk from the Swiss Association against Osteoporosis (SVGO). Swiss Med Wkly 2020; 150: w20352.
- FRAX® Fracture Risk Assessment Tool, www.shef.ac.uk/FRAX (last accessed 03/16/2021).
- Kanis JA, et al: Assessment of fracture risk. Osteoporos Int 2005; 16(6): 581-589.
- Stute P, Meier C: Update osteoporosis. J Gynecol Endocrinol 2021, https://doi.org/10.1007/s41975-021-00181-4
- Bone HG, et al: 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 2017; 5(7): 513-523.
- Watts NB, et al: Safety Observations With 3 Years of Denosumab Exposure: Comparison Between Subjects Who Received Denosumab During the Randomized FREEDOM Trial and Subjects Who Crossed Over to Denosumab During the FREEDOM Extension. J Bone Miner Res 2017; 32(7): 1481-1485.
- Anastasilakis AD, et al: Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial. J Bone Miner Res 2019; 34(12): 2220-2228.
- “Prolia® and Evenity®: How to Prevent Rebound?”, Jan. 28, 2021, www.rheumaliga.ch/blog/2021/prolia-evenity-rebound-effekt, (last accessed Mar. 16, 2021).
- Leder BZ, et al: J Clin Densitom 2016; 19(3): 346-351.
- Swiss Health Observatory (Obsan), www.obsan.admin.ch (last accessed 08.06.2021).
HAUSARZT PRAXIS 2021; 16(7): 20-22
