Hypercalcemia Pathophysiology & Treatment

Medical Treatment of Hypercalcemia

Author(s): Valentina Camozzi, Chiara Franzin and Giovanni Luisetto

Pp: 88-99 (12)

DOI: 10.2174/978160805107611001010088

* (Excluding Mailing and Handling)

Abstract

Hypercalcemia is a relatively common disorder. Primary hyperparathyroidism and malignancy-associated hypercalcemia (MAH) are responsible for more than 90% of all causes of hypercalcemia. General measures of treatment include rehydration and loop diuretics, when renal insufficiency or heart failure is associated. Calcitonin is indicated for the short-term control of severe hypercalcemia, while bisphosphonates are required in the long-term management. The antireabsorptive action of bisphosphonates has been considered the most effective in the disorders characterized by an excessive bone resorption. Both clodronate and pamidronate have been widely used in the past. Recently controlled clinical trials demonstrated the superiority of zoledronate compared with previous treatments. The use of calcimimetic agents has been recently introduced to control hypercalcemia in selected cases of primary hyperparathyroidism. They are used when patients do not meet surgical criteria or surgery is not possible or accepted. Recent studies on cancer-induced bone disease have highlighted the role of receptor activator of nuclear factor-κ ligand (RANKL) as a critical effector of skeletal complications of malignancy. RANKL inhibitors may reduce bone resorption in patients with bone metastases and multiple myeloma. Malignancyassociated hypercalcemia is broadly divided into two categories: humoral MAH and osteolytic MAH. The former refers to the paraneoplastic release of humoral factors, mainly parathyroid hormone-related peptide (PTHrP). A humanized monoclonal antibody against human PTHrP has been generated. It is able to neutralize the PTHrP effects, reducing hypercalcemia in human tumor xenograft animal models.

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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
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      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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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 <= 316312588 and j.to_ip >=316312588 )) and ((j.from_date <= 1740550641 and j.to_date >= 1740550641 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 884) 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 <= 316312588 and j.to_ip >=316312588 )) and ((j.from_date <= 1740550641 and j.to_date >= 1740550641 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 884) 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 <= 316312588 and j.to_ip >=316312588 )) and ((j.from_date <= 1740550641 and j.to_date >= 1740550641 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 884)
      680μsalphaeurekaselec_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` <= 1740550641 and `b`.`banner_to_date` >= 1740550641 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 856
      • 3: 1740550641
      • 4: 1740550641
      • 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='15da7725f41ffd287471ffb15c6eaa1e'
      240μsalphaeurekaselec_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
        Ap9JYPLfx3HNAqAOA3Alj7frVTjE1Ty0BczAEK38
        uc_cart_id
        15da7725f41ffd287471ffb15c6eaa1e
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/884" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/884
        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=eyJpdiI6IlYyMFV4bmY0ZWRSWDh1TlpHSkRtUnc9PSIsInZhbHVlIjoiVk16aHVwSVBKU2ZDdmh1U3Y5azgrTWJTcnUzZjBRT21YVlhPOFFnZ1Urcz0iLCJtYWMiOiJmMjMxYjc2MGI5ZTU3OTljYzJkMjM1Y2MzZjIzYWNhODFiMGZlM2M0ZTMxZmRmZDZlMGViYTJlNGY2NGY5YTY0IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IlYyMFV4bmY0ZWRSWDh1TlpHSkRtUnc9PSIsInZhbHVlIjoiVk16aHVwSVBKU2ZDdmh1U3Y5azgrTWJTcnUzZjBRT21YVlhPOFFnZ1Urcz0iLCJtYWMiOiJmMjMxYjc2MGI5ZTU3" ] "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 => "Wed, 26 Feb 2025 06:17:21 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InVscFRwcFcxaUZuTWp0WFhUMGJZc0E9PSIsInZhbHVlIjoic1JWWXRyL3lBdXVvdWpXQ3AyWWU0UzA5bW9DSS8zWU4zNlRuTnVOLzAzOUtwcXU3NzFnc0ZnbzV5V3RoV1lZUjV1TkE5MjB1Q21TcVBxazRNY3hzNFNrSlZMdnYyS1RaUVk2eU9CL2VUN1dhVWFRT2NNYWlVczdBNXF1cE5vQmEiLCJtYWMiOiI5NDYyZTM4YTRiM2I3YTQ2NWIyNjQ5YjQ4ZmY4Y2E0MTlhMDk1ZWRmMGYxOWFjYWQxYjNjM2Y0MDBiZjBhODIzIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 18:17:21 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InVscFRwcFcxaUZuTWp0WFhUMGJZc0E9PSIsInZhbHVlIjoic1JWWXRyL3lBdXVvdWpXQ3AyWWU0UzA5bW9DSS8zWU4zNlRuTnVOLzAzOUtwcXU3NzFnc0ZnbzV5V3RoV1lZUjV1TkE5M" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjB2T2QyRlk5N3VjL1h4eSs4R2hYaUE9PSIsInZhbHVlIjoiNmg3VndPa0RyazVOdnJhS1BGcHAyMXZITGh1U1kvbUMydzlRQ3FaQmlIcFFZaUlmNDRtT0k3eTNuUWIxQ1V2ckg3NGpmVFhrVWFRcjBwbzBISFlmZ1hIa2JrdDhzRmt6K0RFUDlHbzRCUnluOEtHVFlpY2gzNTRpbk1KSFZaOG0iLCJtYWMiOiJiMTZhYmUyMjhmOTE2MDkzYzNjNDQ5NTkyNDhkOTFjZGE5YmU4NjllZjQ4NzdmN2EwY2Y2YzgwNDE5Y2EyN2NiIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjB2T2QyRlk5N3VjL1h4eSs4R2hYaUE9PSIsInZhbHVlIjoiNmg3VndPa0RyazVOdnJhS1BGcHAyMXZITGh1U1kvbUMydzlRQ3FaQmlIcFFZaUlmNDRtT0k3eTN" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InVscFRwcFcxaUZuTWp0WFhUMGJZc0E9PSIsInZhbHVlIjoic1JWWXRyL3lBdXVvdWpXQ3AyWWU0UzA5bW9DSS8zWU4zNlRuTnVOLzAzOUtwcXU3NzFnc0ZnbzV5V3RoV1lZUjV1TkE5MjB1Q21TcVBxazRNY3hzNFNrSlZMdnYyS1RaUVk2eU9CL2VUN1dhVWFRT2NNYWlVczdBNXF1cE5vQmEiLCJtYWMiOiI5NDYyZTM4YTRiM2I3YTQ2NWIyNjQ5YjQ4ZmY4Y2E0MTlhMDk1ZWRmMGYxOWFjYWQxYjNjM2Y0MDBiZjBhODIzIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 18:17:21 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InVscFRwcFcxaUZuTWp0WFhUMGJZc0E9PSIsInZhbHVlIjoic1JWWXRyL3lBdXVvdWpXQ3AyWWU0UzA5bW9DSS8zWU4zNlRuTnVOLzAzOUtwcXU3NzFnc0ZnbzV5V3RoV1lZUjV1TkE5M" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjB2T2QyRlk5N3VjL1h4eSs4R2hYaUE9PSIsInZhbHVlIjoiNmg3VndPa0RyazVOdnJhS1BGcHAyMXZITGh1U1kvbUMydzlRQ3FaQmlIcFFZaUlmNDRtT0k3eTNuUWIxQ1V2ckg3NGpmVFhrVWFRcjBwbzBISFlmZ1hIa2JrdDhzRmt6K0RFUDlHbzRCUnluOEtHVFlpY2gzNTRpbk1KSFZaOG0iLCJtYWMiOiJiMTZhYmUyMjhmOTE2MDkzYzNjNDQ5NTkyNDhkOTFjZGE5YmU4NjllZjQ4NzdmN2EwY2Y2YzgwNDE5Y2EyN2NiIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjB2T2QyRlk5N3VjL1h4eSs4R2hYaUE9PSIsInZhbHVlIjoiNmg3VndPa0RyazVOdnJhS1BGcHAyMXZITGh1U1kvbUMydzlRQ3FaQmlIcFFZaUlmNDRtT0k3eTN" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "Ap9JYPLfx3HNAqAOA3Alj7frVTjE1Ty0BczAEK38" "uc_cart_id" => "15da7725f41ffd287471ffb15c6eaa1e" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/884" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-26 06:17:21GET/chapter/884112193