Hypercalcemia Pathophysiology & Treatment

Hypercalcemia and Malignancy

Author(s): Umberto Basso, Anna Roma and Antonella Brunello

Pp: 28-37 (10)

DOI: 10.2174/978160805107611001010028

* (Excluding Mailing and Handling)

Abstract

Hypercalcemia arising in cancer patients is usually referred to as malignancy-associated hypercalcemia (MAH). It may complicate early or, more often, late phases of the disease with a prevalence of around 5-30% of all patients with different types of cancer. However, the prophylactic use of bisphosphonates to prevent skeletal events in patients with bone metastases, has probably reduced the occurrence of clinically symptomatic MAH. The most frequent cause of MAH is abnormal production of a parathyroid hormone-related protein (PTHrP), which mimics the effects of parathyroid hormone, increasing bone resorption and, especially, renal tubular calcium reabsorption. Other causes may be bone lysis due to several cytokines and mediators released by the cancer cells in the bone or the ectopic production of 1,25(OH)2 vitamin D3 in tumor tissue. Periodical monitoring of serum ions in cancer patients usually unveils the onset of MAH before the appearance of the classical symptoms (headache, confusion, de-hydration), prompting adequate treatment consisting in hydration, diuretics, bisphosphonates and, whenever possible, treatment of the underlying cancer (usually with systemic chemotherapy). Bisphosphonates are a class of compounds which have all shown to decrease serum calcium levels primarily by inhibition of PTH-dependent osteoclast activation. Although, the antiresorptive potency is higher with late generation compounds (pamidronate, zolendronate, ibandronate) compared to older oral compounds. Agents able to interfere with the receptor activator of nuclear actor-κ ligand (RANKL) pathway such as the monoclonal antibody denosumab represent novel and promising strategies for the treatment of MAH which are currently undergoing experimental and clinical assessment.

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      • 11. app/Models/ContentAccess.php:647
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      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59081319 and j.to_ip >=59081319 )) and ((j.from_date <= 1740526723 and j.to_date >= 1740526723 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 879) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59081319 and j.to_ip >=59081319 )) and ((j.from_date <= 1740526723 and j.to_date >= 1740526723 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 879) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59081319 and j.to_ip >=59081319 )) and ((j.from_date <= 1740526723 and j.to_date >= 1740526723 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 879)
      530μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 856 and `b`.`banner_from_date` <= 1740526723 and `b`.`banner_to_date` >= 1740526723 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 856
      • 3: 1740526723
      • 4: 1740526723
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='88f0ed047d646a04b8b3d96ec93a8108'
      210μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Keywords
    1Keywords.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        lSVQiB9COTQp7fTHN1qRNTj2w2kjGhmxQVO4q6mw
        uc_cart_id
        88f0ed047d646a04b8b3d96ec93a8108
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/879" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/879
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InlNaXFhcis0cld0YW1lYjZ3cE9QNVE9PSIsInZhbHVlIjoidi9qNFc5MHlsQ2pSRmd0ZHNaUDRXOVVVWks4NU8zdFNyQWppbG9DZ3ZpQT0iLCJtYWMiOiJiMzI5NjAxNTRjMTA0NWEzZTkyNTRkMDU4ZGQ5Mzk1NmIzMDNlNzgwZjY0OTJhZGQ4NTVkZWMwODVkMWNkMThkIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InlNaXFhcis0cld0YW1lYjZ3cE9QNVE9PSIsInZhbHVlIjoidi9qNFc5MHlsQ2pSRmd0ZHNaUDRXOVVVWks4NU8zdFNyQWppbG9DZ3ZpQT0iLCJtYWMiOiJiMzI5NjAxNTRjMTA0" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 23:38:43 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InB2V25FbE9LbFFqYkZVRlpJbjBPRnc9PSIsInZhbHVlIjoieENmWkE3bjdhaGpGRVZZVzlRTUcrd3ZCRDNiZnRnUGpGempQYUFBT0YxVkJOZzg3VnllazBiWm5aR1JTTXgxSW9wemxlY1pBOTdmWVZxNlFEaVRQSEcwaThXU1JPbVI4Ny93dEs0SU43T0RYMFpwSTNLQUJaWTZqNUU3clQ5SysiLCJtYWMiOiJmYThjMGY3MzFmNWFhYTJhYmEwNmMyZDE1Y2JjZTllZTQ2MWI5MDI2MmRmNjRlOTg2YTc5MjNmNTExYzlmYzkwIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 11:38:43 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InB2V25FbE9LbFFqYkZVRlpJbjBPRnc9PSIsInZhbHVlIjoieENmWkE3bjdhaGpGRVZZVzlRTUcrd3ZCRDNiZnRnUGpGempQYUFBT0YxVkJOZzg3VnllazBiWm5aR1JTTXgxSW9wemxlY" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlZhZFN0N2VENFhRamo4ZzhmWGZhMUE9PSIsInZhbHVlIjoiSHRybWlYaE9mejdaUWpRT3RUK3lMbFlROVVRWWRBQlJVOENHdTJ3WGg1eW04TkZvY3d1bSsvYTJyTXlkVkM0eStkRURIbzVwRS9iWXA1cVQ5UnpMODcrNWtRdytnQjMzVVFLQTQxcExJU0tsYmZGTzB1TTJEQ1N0ZkFTc2lCZlgiLCJtYWMiOiIxOGMxMWQ5OGQzMDNmZWQ3ZWFmZmQ0YmY2ZGU3ZGYwYjRkN2MzN2UyYjUxZWQ3NzdmMmI1NjRhN2M4ODQ1M2Y3IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlZhZFN0N2VENFhRamo4ZzhmWGZhMUE9PSIsInZhbHVlIjoiSHRybWlYaE9mejdaUWpRT3RUK3lMbFlROVVRWWRBQlJVOENHdTJ3WGg1eW04TkZvY3d1bSsvYTJ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InB2V25FbE9LbFFqYkZVRlpJbjBPRnc9PSIsInZhbHVlIjoieENmWkE3bjdhaGpGRVZZVzlRTUcrd3ZCRDNiZnRnUGpGempQYUFBT0YxVkJOZzg3VnllazBiWm5aR1JTTXgxSW9wemxlY1pBOTdmWVZxNlFEaVRQSEcwaThXU1JPbVI4Ny93dEs0SU43T0RYMFpwSTNLQUJaWTZqNUU3clQ5SysiLCJtYWMiOiJmYThjMGY3MzFmNWFhYTJhYmEwNmMyZDE1Y2JjZTllZTQ2MWI5MDI2MmRmNjRlOTg2YTc5MjNmNTExYzlmYzkwIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 11:38:43 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InB2V25FbE9LbFFqYkZVRlpJbjBPRnc9PSIsInZhbHVlIjoieENmWkE3bjdhaGpGRVZZVzlRTUcrd3ZCRDNiZnRnUGpGempQYUFBT0YxVkJOZzg3VnllazBiWm5aR1JTTXgxSW9wemxlY" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlZhZFN0N2VENFhRamo4ZzhmWGZhMUE9PSIsInZhbHVlIjoiSHRybWlYaE9mejdaUWpRT3RUK3lMbFlROVVRWWRBQlJVOENHdTJ3WGg1eW04TkZvY3d1bSsvYTJyTXlkVkM0eStkRURIbzVwRS9iWXA1cVQ5UnpMODcrNWtRdytnQjMzVVFLQTQxcExJU0tsYmZGTzB1TTJEQ1N0ZkFTc2lCZlgiLCJtYWMiOiIxOGMxMWQ5OGQzMDNmZWQ3ZWFmZmQ0YmY2ZGU3ZGYwYjRkN2MzN2UyYjUxZWQ3NzdmMmI1NjRhN2M4ODQ1M2Y3IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlZhZFN0N2VENFhRamo4ZzhmWGZhMUE9PSIsInZhbHVlIjoiSHRybWlYaE9mejdaUWpRT3RUK3lMbFlROVVRWWRBQlJVOENHdTJ3WGg1eW04TkZvY3d1bSsvYTJ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "lSVQiB9COTQp7fTHN1qRNTj2w2kjGhmxQVO4q6mw" "uc_cart_id" => "88f0ed047d646a04b8b3d96ec93a8108" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/879" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 23:38:43GET/chapter/879112193