Spine and hip fractures can be prevented with proper medical management in elderly population
Osteoporosis is the most common skeletal disease in elderly. As we age our bone microarchitecture and bone mass deteriorates leading to increase fracture risk. This is due to increased bone resorption and reduced bone formation, therefore predisposing to fractures even with trivial trauma.
The treatment of osteoporosis can be classified as antiresorptive and osteoanabolic.
The antiresorptive agents primarily reduce osteoclastic activity and these include hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), bisphosphonates (BPs), and denosumab (Dmab).
The osteoanabolic agents primarily stimulate osteoblast differentiation, function and survival, and include teriparatide (TPTD), abaloparatide (ABL), and romosozumab (ROMO).
It should bestressed out that the latter i.e romosozumab displays dual actions, combiningboth osteoanabolic and antiresorptive effects; however, it istypically classified as an osteoanabolic agent.
Dmab should be preferred in patients with impaired renal function. Furthermore, it is effective across a broad range of subjects with estimated glomerular filtration rate (GFR) as low as 15mL/min, and its effect on fracture risk reduction is not associated with the level of renal function.
Bisphosphonates are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow. Give bisphosphonates like zolindronic acid infusion 2 months after stopping Dmab. Delaying administration of iv BPs might increase their skeletal uptake resulting in improved retention of the bone architecture achieved with Dmab.
So, in ambulatory patients with normal renal function, it is probably better to start treatment with a BP for 5 years and reconsider. Dmab instead is an excellent choice in cases of upper gastrointestinal problems, bisphosphonates treatment failure or even in subjects needing continuation of osteoporosis treatment after some years under Bisphosphonates. In patients with very low BMD, patients with renal impairment, and elderly subjects with polypharmacy it seems better to initiate treatment with Dmab.
Combination therapy is not generally recommended, nor approved by health care systems, but may be considered for patients at high risk of fractures already on treatment with antiresorptives (BPs & Dmabs) . In particular, in the case of very high fracture risk, e.g. an incident of new vertebral fractures during Dmab therapy, the Swiss Association against osteoporosis (SVGO/ASCO) recommends combination therapy with Teraperitide (TPTD) for 24 months followed by antiresorptive therapy for another 12–24 months. Among combination treatment options, available evidence depicts the combination of TPTD with Dmab as the most effective, followed by the combination of TPTD with zolindronic acid. The optimal approach for a patient with severe osteoporosis would be to initiate with an osteoanabolic agent and then transit to an antiresorptive one.
Although the use of PTH analogs, for example, teraperitide is common in non-responders to antiresorptives, this might not be the optimal sequence of antiosteoporotic treatment, as it could result in a transient loss of hip BMD and strength. Sequential use of teraperitide should be carefully considered in high-risk patients previously treated with BPs or Dmab.
Sequential treatment with BPs or Dmab is important to maintain or even increase bone mass and possibly improve mineralization in patients previously treated with osteoanabolic medications. So we need to start Dmab or BPs within 6 months of stopping Teraperitide (TPTD) to maintain BMD gains.
In a previous trial published in 2013, the Denosumab and Teriparatide Administration (DATA) study, the same authors looked at the same combination and found denosumab was able to fully inhibit the effects of bone resorption induced by teriparatide while allowing for bone formation by teriparatide, boosting the effects on hip and spine BMD compared with either drug alone”.
Side effects:
Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. These side effects are seen in patients with certain risk factors like prior glucocorticoid use, chemotherapy use, invasive dental procedure, and older age.In some cases severe symptomatic hypocalcemia ; most events occurred within 30 days of Dmab administration.Majority of these patients are of chronic kidney disease and they respond to calcium and Vit D. Therefore, early and closer monitoring of serum Calcium is warranted in patients with renal failure treated with Dmab. Finally, few reports of medically confirmed anaphylaxis, most of which occurred the first day of the first Dmab dose.
The most common adverse events of teraperitide were joint pain, fatigue and nausea.
To conclude, I just want to emphasize that we need to personalize treatments for osteoporosis depending on patients risk profile and comorbidities, beyond the one-size-fits-all approach currently used. (i.e predominantly prescribing bisphosphonates)”
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