Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?

Tsvetov, Gloria; Amitai, Oren; Shochat, Tzippy; Shimon, Ilan; Akirov, Amit; Diker-Cohen, Talia

doi:10.1007/s00198-019-05261-7

Cited by 47 publications

(43 citation statements)

References 38 publications

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“…Low pre-treatment levels of serum calcium have been reported as a risk factor for hypocalcaemia 15 . Our result was also in agreement with those of previous studies.…”

Section: Discussionmentioning

confidence: 99%

Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis

Kanbayashi

Sakaguchi

Hongo

et al. 2021

Sci Rep

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This retrospective study was undertaken to identify predictors for the development of hypocalcaemia even with prophylactic administration of calcium and vitamin D, and to help guide future strategies to improve the safety, efficacy, and QOL of patients receiving denosumab. Between January 2016 and February 2020, a total of 327 advanced cancer patients at our hospital who were receiving denosumab were enrolled. Variables associated with the development of hypocalcaemia were extracted from the clinical records. The level of hypocalcaemia was evaluated using CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictors for the development of hypocalcaemia. Optimal cut off thresholds were determined using ROC analysis. Values of P < 0.05 (2-tailed) were considered significant. 54 patients have developed hypocalcemia (≥ Grade 1). Significant factors identified included concomitant use of vonoprazan [odds ratio (OR) = 3.74, 95% confidence interval (CI) 1.14–12.26; P = 0.030], dexamethasone (OR = 2.45, 95%CI 1.14–5.42; P = 0.022), pre-treatment levels of serum calcium (OR = 0.27, 95%CI 0.13–0.54; P < 0.001), ALP/100 (OR = 1.04, 95%CI 1.01–1.07; P = 0.003), and haemoglobin (OR = 0.79, 95%CI 0.68–0.93; P = 0.004). ROC curve analysis revealed that the threshold for pre-treatment levels of serum calcium was ≤ 9.3 mg/dL, ALP was ≥ 457 U/L, and haemoglobin was ≤ 10.4 g/dL. In conclusion, concomitant use of vonoprazan or dexamethasone, and pre-treatment levels of serum calcium (low), ALP (high) and haemoglobin (low) were identified as significant predictors for the development of denosumab-induced hypocalcaemia.

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“…Low pre-treatment levels of serum calcium have been reported as a risk factor for hypocalcaemia 15 . Our result was also in agreement with those of previous studies.…”

Section: Discussionmentioning

confidence: 99%

Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis

Kanbayashi

Sakaguchi

Hongo

et al. 2021

Sci Rep

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“…Denosumab is a human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL). RANKL is a receptor expressed on the surface of cells of the osteoclast lineage, produced by osteoblasts that interact with RANK [ 49 ]. Denosumab could mimic the action of osteoprotegerin (a natural decoy receptor of RANKL), thereby blockading the RANKL-RANK interaction and inhibiting osteoclast action and bone resorption [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…RANKL is a receptor expressed on the surface of cells of the osteoclast lineage, produced by osteoblasts that interact with RANK [ 49 ]. Denosumab could mimic the action of osteoprotegerin (a natural decoy receptor of RANKL), thereby blockading the RANKL-RANK interaction and inhibiting osteoclast action and bone resorption [ 49 ]. Treatment with denosumab has been found to increase BMD, and long-term therapy has been associated with a lower rate of bone fractures [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Seasonal Variation and Global Public Interest in the Internet Searches for Osteoporosis

Wang

Xiong

Tao

et al. 2021

BioMed Research International

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Background. To ascertain the seasonal pattern and global public interest in osteoporosis by evaluating search term popularity changes of the disease over a decade. Methods. We applied Google Trends to retrieve search popularity scores for the term “osteoporosis” between January 01, 2004, and December 31, 2019. Cosinor analyses were conducted to examine the seasonality of osteoporosis, and analysis on osteoporosis-related topics including hot topics and rising-related topics was also performed. Results. The cosinor analyses demonstrated a statistically significant seasonal variation in relative search volume of the “osteoporosis” in the world ( p = 0.0083 ), USA ( p < 0.001 ), UK ( p < 0.001 ), Canada ( p < 0.001 ), Ireland ( p < 0.001 ), Australia ( p < 0.001 ), and New Zealand ( p < 0.001 ), with a peak in the late winter months and trough in the summer months. The peaks in late winter and valley in summer presented an approximately 6-month difference between hemispheres. The top 11 rising topics were denosumab, FRAX, hypocalcaemia, zoledronic acid, ibandronic acid, osteomyelitis, osteopenia, osteoarthritis, bone, calcium, and bone density. Conclusions. Google search query volumes related to osteoporosis follow strong seasonal patterns with late winter peaks and summer troughs. Further studies aimed at elucidating the possible mechanisms behind seasonality in osteoporosis are needed. Moreover, Internet data including the top rising topics may alert physicians to strengthen the propaganda of osteoporosis timely, so as to further promote the development of public health interventions.

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“…Denosumab inhibits osteoclastic bone resorption and causes an imbalance in osteoclast and osteoblastic activity, leading to hypocalcemia by reducing calcium mobilization from the bone [ 12 ]. Some studies have reported that high bone turnover is associated with a higher risk of denosumab-induced hypocalcemia [ 10 , 11 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

Denosumab-induced hypocalcemia in a patient with hyperthyroidism: a case report

Park

Kim²,

Chung

2021

Osteoporos Int

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Denosumab is a humanized monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab is an effective treatment for osteoporosis but can cause hypocalcemia. We present a case of denosumab-induced hypocalcemia in a patient with hyperthyroidism with a high bone turnover state. A 48-year-old postmenopausal woman was diagnosed with hyperthyroidism and osteoporosis and received antithyroid drugs (propylthiouracil 200 mg/day) and denosumab. After 2 months of taking medication, the patient complained of numbness and tingling in the hands and feet and was diagnosed with hypocalcemia (calcium, 5.8 mg/dL; ionized calcium, 0.83 mmol/L). Alfacalcidol (0.5 μg/day) and calcium carbonate (3000 mg/day) were prescribed. Subsequently, the patient’s symptoms improved, and her serum calcium level normalized. The risk of denosumab-induced hypocalcemia may be increased in patients with diseases related to high bone turnover, such as hyperthyroidism; therefore, caution is needed.

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Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?

Cited by 47 publications

References 38 publications

Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis

Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis

Seasonal Variation and Global Public Interest in the Internet Searches for Osteoporosis

Denosumab-induced hypocalcemia in a patient with hyperthyroidism: a case report

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