A meta-analysis of the efficacy of 99Tc-MDP alone and in combination with 89SrCl2 in the treatment of bone metastases

doi:10.19401/j.cnki.1007-3639.2023.08.004

Abstract

Abstract:

Background and purpose: Bone metastatic tumor is a common disease of tumor bone metastasis, and the prognosis of patients is poor, with a variety of serious complications, including bone pain, fracture, spinal cord compression and other skeletal related events, affecting the quality of life of patients. At present, radionuclide therapy still has positive clinical effects in patients with bone metastasis, and it still plays an important role in relieving bone pain. This study aimed to evaluate the efficacy of technetium [⁹⁹Tc] methylene diphosphonate injection (⁹⁹Tc-MDP) alone or in combination with strontium chloride (⁸⁹SrCl₂) in the treatment of bone metastases. Methods: Databases were used to search for studies published between January 2000 and July 2022 on the efficacy of ⁹⁹Tc-MDP in combination with ⁸⁹SrCl₂ and ⁹⁹Tc-MDP alone in the treatment of bone metastases. All included literature was extracted and evaluated for quality, and Meta-analysis was performed using RevMan 5.3 software. Results: Twenty-seven publications met the inclusion criteria, and a total of 2564 patients were included in this study. The results demonstrated that ⁹⁹Tc-MDP combined with ⁸⁹SrCl₂ improved bone pain relief (RR=1.22, 95% CI: 1.18-1.27, P<0.001) and bone metastasis healing (RR=1.35, 95% CI: 1.25-1.47, P<0.001). However, when compared with ⁸⁹SrCl₂ alone, it could not be concluded that ⁹⁹Tc-MDP alone increased the rate of bone pain relief (RR=0.98, 95% CI: 0.90-1.06, P=0.57) and bone metastasis healing (RR=0.93, 95% CI: 0.82-1.06, P=0.27), and the difference between the two groups was not statistically significant. The common adverse effects of ⁹⁹Tc-MDP treatment alone or in combination with ⁸⁹SrCl₂ were decreased leukocyte and platelet counts, however, the difference in the incidence of adverse effects between ⁹⁹Tc-MDP treatment alone and in combination with ⁸⁹SrCl₂ was not statistically significant (⁸⁹SrCl₂ vs ⁹⁹Tc-MDP in combination with ⁸⁹SrCl₂: RR=0.83, 95% CI: 0.53-1.30, P=0.42; ⁸⁹SrCl₂ vs ⁹⁹Tc-MDP: RR=0.93, 95% CI: 0.76-1.13, P=0.45). Conclusion: ⁹⁹Tc-MDP combined with ⁸⁹SrCl₂ treatment was effective in relieving pain in patients with bone metastases, and the bone pain relief rate and bone metastasis healing rate of ⁹⁹Tc-MDP combined with ⁸⁹SrCl₂ treatment for bone metastases were better compared with the ⁸⁹SrCl₂ monotherapy group, with no significant increase in adverse reactions after typical dosing. Due to the limitations of the quality and quantity of literature included in this study, higher quality randomized controlled studies are needed.

Key words: Bone metastasis, ⁹⁹Tc-MDP, ⁸⁹SrCl₂, Meta-analysis

CLC Number:

R730.53

CHEN Man, ZENG Feiyan, LI Qingqing, LI Hongdan, LIN Yansong, FENG Ping. A meta-analysis of the efficacy of ⁹⁹Tc-MDP alone and in combination with ⁸⁹SrCl₂ in the treatment of bone metastases[J]. China Oncology, 2023, 33(8): 751-767.

Figures/Tables 14

Fig. 1

Tab. 1

Characteristics of included studies"

Study/published year	Cancer	Evaluation	Group	Mean age/year	Gender (female)	Case n	Treatment	AE
Sang S B, et al^[28]2001	Lung cancer, prostate cancer, breast cancer, nasopharyngeal cancer, rectal cancer, and cancers of unknown origin	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	55.0	41.2%	38	⁸⁹SrCl₂ 150 MBq, 5 patients received a second injection, all with an interval of more than 3-6 months	White blood cells and platelets decreased slightly in some patients, most of which occurred 4-8 weeks after treatment, but they all recovered to the pre-treatment level during follow-up. Transient pain intensification occurred in very few patients after treatment, and most of them disappeared after 3 to 7 days of treatment
Sang S B, et al^[28]2001		Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂	55.0	41.2%	30	⁸⁹SrCl₂ 150 MBq, ⁹⁹Tc-MDP 200 mg/d, 5d as a course, 2-3 courses
Zhong G P, et al^[39]2002	Prostate cancer, kidney cancer, bladder cancer, testicular cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	60.9	15.2%	16	⁸⁹SrCl₂ 1.48-2.22 MBq/kg	Transient bone pain was aggravated in some patients after treatment, which was relieved with painkillers and gradually alleviated 2-4 days later. A small number of cases showed hematological grade Ⅰ to Ⅱ toxic reactions. White blood cell count and platelet count decreased 1-2 weeks later, and decreased to the lowest level (lower limit of normal value) in 1 month, then gradually recovered to the pre-treatment level within 2-5 weeks
			⁹⁹Tc-MDP			9	⁹⁹Tc-MDP 200 mg/d, 5 d as a course. The second course of treatment was performed at an interval of 10 d, 4 courses
			⁹⁹Tc-MDP+⁸⁹SrCl₂			8	One course of ⁹⁹Tc-MDP by intravenous drip, followed by one dose of ⁸⁹SrCl₂ by intravenous injection after 3 to 5 d
Mo Y, et al^[24]2004	Breast cancer, lung cancer, prostate cancer and other malignancies	Rate of relief of bone pain	⁸⁹SrCl₂	56.0	41.2%	51	⁸⁹SrCl₂ 111-148 MBq (3-4 mci), every 3 to 6 months	No serious toxic and side effects were observed in both groups. After treatment with ⁸⁹SrCl₂, a small number of patients showed inhibition of bone marrow. hematopoietic function, manifested by decreased white blood cell and platelet counts. It will return to normal in about 4 to 6 weeks. There was no obvious damage to liver and kidney function
	Breast cancer, lung cancer, nasopharyngeal cancer and other malignant tumors		⁹⁹Tc-MDP+⁸⁹SrCl₂	50.0	59.3%	54	⁸⁹SrCl₂ 111-148 MBq (3-4 mci), every 3 to 6 months; ⁹⁹Tc-MDP 200 mg/d, 5 d as a course
Li J G, et al^[20]2004	Breast cancer, lung cancer, prostate cancer, esophageal cancer, cardiac cancer, cervical cancer, nasopharyngeal cancer, rectal cancer, liver cancer and others	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	Male 56.5 Female 50.5	46.2%	55	⁸⁹SrCl₂ 130-174 MBq	In terms of liver function, 14 patients showed increased single index
Li J G, et al^[20]2004		Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂	Male 56.5 Female 50.5	46.2%	51	⁸⁹SrCl₂ 130-174 MBq. After 20 d, injecting ⁹⁹Tc-MDP 200 mg intravenously for more than 3 h, 5 days as a course of treatment; or 3 h intravenously for 10 days as a course of treatment. One course of treatment per month for 2 to 3 consecutive courses.	In terms of liver function, 12 patients showed increased single index
Shi G Q, et al^[30]2006	Prostate cancer, lung cancer, breast cancer, rectal cancer and malignancies of unknown primary	Rate of relief of bone pain	⁸⁹SrCl₂	62.3	33.3%	24	⁸⁹SrCl₂ 2.6 MBq/kg.	In blood images, mildly affected: 18, moderately affected: 4, severely affected: 2
Shi G Q, et al^[30]2006		Rate of relief of bone pain	⁹⁹Tc-MDP+⁸⁹SrCl₂	58.6	20.8%	24	⁸⁹SrCl₂ 2.6 MBq/kg; ⁹⁹Tc-MDP 5 mg/d	In blood images, mildly affected: 17, moderately affected: 4, severely affected: 3
Shi F, et al^[29]2006	Breast cancer, lung cancer, prostate cancer, and other malignancies	Rate of relief of bone pain	⁸⁹SrCl₂	50.0	40.8%	71	⁸⁹SrCl₂ 1.48-2.22 MBq/kg (40-60 uci)	No serious side effects were observed. Bone pain was aggravated in a small number of patients 2-4 days after treatment, but no special treatment was done. A few patients showed inhibition of bone marrow hematopoietic function, leukocyte and platelet decline, about 4-6 weeks later returned to normal, no significant damage to liver and kidney function
Shi F, et al^[29]2006	Breast cancer, lung cancer, nasopharyngeal cancer and other malignant tumors.		⁹⁹Tc-MDP+⁸⁹SrCl₂	47.0	55.4%	74	⁸⁹SrCl₂ 1.48-2.22 MBq/kg (40-60 uci); ⁹⁹Tc-MDP 200 mg/d, 5 days for a course
Ren H, et al^[27]2008	Lung cancer, breast cancer, prostate cancer, rectal cancer, stomach cancer	Rate of relief of bone pain	⁸⁹SrCl₂	67.2	38.7%	31	⁸⁹SrCl₂ 1.48-2.22 MBq/kg, once every 3 months	In the two groups, 22.5% and 24.2% of the cases had grade Ⅰ -Ⅱ leukopenia, and 16.1% and 21.2% of the cases had grade Ⅰ - Ⅱ thrombocytopenia, respectively. There was no statistically significant difference between the two groups. Hematological toxicity usually appears at 4-6 weeks and recovers after 2-3 weeks, mainly as platelet and leukocyte reduction
Ren H, et al^[27]2008	Lung cancer, breast cancer, prostate cancer, rectal cancer, stomach cancer, ovarian cancer.		⁹⁹Tc-MDP+⁸⁹SrCl₂	63.6	48.5%	33	⁸⁹SrCl₂ 1.48-2.22 MBq/kg, once every three months; ⁹⁹Tc-MDP 11mg/d, 7 days for a course of treatment, once a month
Guan R G, et al^[18] 2008	Lung cancer, breast cancer, nasopharyngeal cancer, prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	46.0	48.1%	27	⁸⁹SrCl₂ 111-148 MBq	Only 2 patients developed skeletal depression, transient hypoleucopenia, toxicity evaluation was Ⅱ degree, untreated, spontaneous recovery after 2 weeks
	Lung cancer, breast cancer, nasopharyngeal cancer, cervical cancer		⁹⁹Tc-MDP+⁸⁹SrCl₂	47.0	58.6%	29	⁸⁹SrCl₂ 111-148 MBq. After 3 d, injecting ⁹⁹Tc-MDP 20 mg intravenously once a day for 5 d, followed by ⁹⁹Tc-MDP 5mg intravenously for 15 d
Wang J F, et al^[31] 2009	61 cases of breast cancer, 52 cases of prostate cancer, 45 cases of lung cancer, thyroid cancer, nasopharyngeal cancer, rectal cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	53.0	41.2%	45	⁸⁹SrCl₂ 148 MBq	After treatment, a small number of patients felt general fatigue, nausea and other symptoms, some patients slightly decreased, a very small number of patients showed transient pain exacerbation after treatment
			⁹⁹Tc-MDP			38	⁹⁹Tc-MDP 200 mg/d, 5 days for a course, once a month, for 2-3 courses
			⁹⁹Tc-MDP+⁸⁹SrCl₂			82	⁸⁹SrCl₂ 148 MBq; ⁹⁹Tc-MDP 200 mg/d, 5 days for a course, once a month, for 2-3 courses
Zhang J H, et al^[35] 2010	Breast cancer, lung cancer, nasopharyngeal cancer, and other tumors	Rate of relief of bone pain	⁸⁹SrCl₂	52.0	61.7%	60	⁸⁹SrCl₂ 111-148 MBq (3-4 mci) every 3-6 months	There was no significant difference between the groups
Zhang J H, et al^[35] 2010		Rate of relief of bone pain	⁹⁹Tc-MDP+⁸⁹SrCl₂	49.0	57.4%	61	⁸⁹SrCl₂ 111-148 MBq (3-4 mci) every 3-6 months; ⁹⁹Tc-MDP 200 mg/d, 5 days for a course	There was no significant difference between the groups
Ning S F, et al^[26] 2010	Lung cancer, breast cancer, prostate cancer, nasopharyngeal cancer, rectal cancer, stomach cancer, uterine cancer	Rate of relief of bone pain	⁸⁹SrCl₂	66.3	44.6%	65	⁸⁹SrCl₂ 1.48-2.22 MBq/kg, every 3 mouths	In the two groups, 20% and 22.6% of the cases showed mild to moderate leukopenia, and 15.4% and 17% of the cases showed mild to moderate thrombocytopenia. Single decline was more common, and one case in both groups had severe leukopenia and thrombocytopenia
Ning S F, et al^[26] 2010	Lung cancer, breast cancer, prostate cancer, nasopharyngeal cancer, rectal cancer, ovarian cancer	Rate of relief of bone pain	⁹⁹Tc-MDP+⁸⁹SrCl₂	61.5	52.8%	53	⁸⁹SrCl₂ 1.48-2.22 MBq/kg, every 3 mouths; ⁹⁹Tc-MDP 15 mg/d, 10 days for a course
Zhu W R, et al^[40] 2011	Prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	63.2±7.6	0.0%	46	⁸⁹SrCl₂ 148-185 MBq	There were no adverse reactions in the two groups
Zhu W R, et al^[40] 2011	Prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂			49	⁸⁹SrCl₂ 148-185 MBq; ⁹⁹Tc-MDP 22 mg/d, 10 days for a course, for 3-5courses	There were no adverse reactions in the two groups
Chen M, et al^[15] 2011	Breast cancer	Rate of relief of bone pain	⁸⁹SrCl₂	43.5	100.0%	45	⁸⁹SrCl₂ 1.48-2.22 MBq/kg (40-60 uCi)/kg	Leukocytosis of grade 1 in 4 cases and grade 2 in 1 case; Grade 1 thrombocytopenia in 5 patients
Chen M, et al^[15] 2011	Breast cancer	Rate of relief of bone pain	⁹⁹Tc-MDP+⁸⁹SrCl₂			42	⁸⁹SrCl₂ 1.48-2.22 MBq/kg (40-60 uCi)/kg; ⁹⁹Tc-MDP 5 mg/d, 15 days for a course	Leukocytosis of grade 1 in 3 cases; 2 cases of grade 1 thrombocytopenia
Dong Z F, et al^[16] 2012	Lung squamous cell carcinoma, lung adenocarcinoma, small cell lung cancer, lung adeno-squamous cell carcinoma	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	50.0	25.7%	33	⁸⁹Sr 1.48 × 10⁸ Bq	Hematotoxic reaction (17 cases of degree 1, 3 cases of degree 2, 0 cases of degree 3)
Dong Z F, et al^[16] 2012		Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂	52.0	33.3%	30	⁸⁹Sr 1.48 × 10⁸ Bq; ⁹⁹Tc-MDP 25 mg/d, 15 days for a course	Hemotoxic reaction (11 cases of degree 1, 2 cases of degree 2, 0 cases of degree 3)
Ning J H, et al^[25] 2014	Lung cancer, breast cancer, prostate cancer, stomach cancer, bladder cancer, nasopharyngeal cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	56.0	44.4%	54	⁸⁹Sr 4 mci	Aggravation of bone pain occurred in 18 cases
			⁹⁹Tc-MDP+⁸⁹SrCl₂			54	⁸⁹Sr 4 mci; ⁹⁹Tc-MDP 22 mg/d, 10 days for a course, for 3 courses	Aggravation of bone pain occurred in 12 cases
Zhu W R, et al^[40] 2015	Breast cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	61.5	Not described	42	⁸⁹SrCl₂ 1.48-2.22 MBq/kg	There were no adverse reactions in the two groups
		Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂			45	⁸⁹SrCl₂ 1.48-2.22 MBq/kg; ⁹⁹Tc-MDP 22 mg/d, 10 days for a course, for 3 courses	There were no adverse reactions in the two groups
Yang J, et al^[34] 2015	Prostate cancer, lung cancer, breast cancer	Rate of relief of bone pain	⁸⁹SrCl₂	56.0±13.3	27.6%	63	⁸⁹SrCl₂ 148 MBq (4 raci)	The bone pain of 3 patients worsened 3-7 days after treatment, and was self-alleviated 1 week later. White blood cells and platelets decreased for 4-6 weeks and recovered to normal. There were no significant changes in liver and kidney function
	Prostate cancer, lung cancer, breast cancer	Rate of relief of bone pain	⁹⁹Tc-MDP+⁸⁹SrCl₂			64	⁸⁹SrCl₂ 148 MBq (4 raci); ⁹⁹Tc-MDP 33 mg/d, for 5 days
Xie C H, et al^[32] 2015	Lung cancer, stomach cancer, breast cancer, and other malignancies	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	55.1±6.3	47.6%	63	⁸⁹SrCl₂ 2.22 MBq/kg	Leukopenia and thrombocytopenia: 5 patients, elevated transaminase: 3 patients, fever, nausea, vomiting and other symptoms: 5 patients
		Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂	56.7±6.9	44.4%	63	⁸⁹SrCl₂ 2.22 MBq/kg; ⁹⁹Tc-MDP 200 mg/d, 5 days for a course, once a month, for 2-3 courses	Leukopenia and thrombocytopenia: 3 patients, elevated transaminase: 4 patients, fever, nausea, vomiting and other symptoms: 9 patients
Liu H C, et al^[32] 2015	Breast cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	56.4±13.8	100.0%	30	⁸⁹SrCl₂ 1.48-1.85 MBq/kg	Leukocyte and/or platelet decreased in 5 cases
			⁹⁹Tc-MDP	51.6±11.7		22	⁹⁹Tc-MDP 16.5 mg/d, 6 days for a course, once a month, for 2-3 courses	No adverse reaction
			⁹⁹Tc-MDP+⁸⁹SrCl₂	54.1±12.1		28	⁸⁹SrCl₂ 1.48-1.85 MBq/kg; ⁹⁹Tc-MDP 16.5 mg/d, 6 days for a course, once a month, for 2-3 courses	Leukocyte and/or platelet decreased in 4 cases
Xu R S, et al^[33] 2016	Prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	71.5	0.0%	47	⁸⁹SrCl₂ 148 MBq	Most of the patients showed transient decrease in WBC and PLT, which could recover to normal by itself. 4 patients showed low white blood cell count, which recovered to normal after symptomatic treatment
	Prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂			50	⁸⁹SrCl₂ 148 MBq; ⁹⁹Tc-MDP 1 time/d for 10 d for 1 cycle. 1 cycle of treatment per month, 3 times in a row for 1 course of treatment
Huang Y, et al^[19]2017	Prostate cancer, lung cancer, breast cancer, endometrial cancer, nasopharyngeal cancer, liver cancer, rectal cancer, and other types of malignant tumors	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	62.1±13.2	35.1%	111	⁸⁹SrCl₂ 4 mci/d, 10 days for a course, for 3 courses	Pain: 18 cases; leukopenia: 22 cases; thrombocytopenia: 17 cases; allergic reaction: 8 cases; gastrointestinal reaction: 2 cases
			⁹⁹Tc-MDP	59.7±13.7	35.4%	130	⁹⁹Tc-MDP 5.5 mg/d, 5 days for a course, for 3 courses	Pain: 22 cases; leukopenia: 28 cases; thrombocytopenia: 20 cases; allergic reaction: 7 cases; gastrointestinal reaction: 5 cases
			⁹⁹Tc-MDP+⁸⁹SrCl₂	62.1±13.2	31.3%	160	⁸⁹SrCl₂ 4 mci/d, 10 days for a course, for 3 courses; ⁹⁹Tc-MDP 22 mg/d, 10 days for a course, for 3 courses	Pain: 13 cases; leukopenia: 14 cases; thrombocytopenia: 10 cases; allergic reaction: 5 cases; gastrointestinal reaction: 1 case
Zhao D D, et al^[38] 2017	Left breast cancer, right breast cancer	Rate of relief of bone pain	⁸⁹SrCl₂	51.1±7.2	Not described	42	⁸⁹SrCl₂ 1.48-1.85 MBq/kg	Thrombocytopenia: 3 cases; leukopenia: 4 cases
	Left breast cancer, right breast cancer, bilateral breast cancer		⁹⁹Tc-MDP+⁸⁹SrCl₂	50.0±6.9		44	⁸⁹SrCl₂ 1.48-1.85 MBq/kg; ⁹⁹Tc-MDP 100 mg/d，6 days for a course, once a month, for 3 courses	Thrombocytopenia: 4 cases; leukopenia: 6 cases
Zhang W, et al^[37]2019	Prostate cancer, lung cancer, breast cancer, endometrial cancer, liver cancer, nasopharyngeal cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	55.6±3.3	42.3%	26	⁸⁹SrCl₂ 4 mci/d, 10 days for a course	4 cases (pain, leukopenia, thrombocytopenia, allergic reaction, gastrointestinal reaction)
			⁹⁹Tc-MDP	56.3±3.5	38.5%	26	⁹⁹Tc-MDP 5.5 mg/d, intravenously, 5 days for a course	3 cases (pain, leukopenia, thrombocytopenia, allergic reaction, gastrointestinal reaction)
			⁹⁹Tc-MDP+⁸⁹SrCl₂	57.6±3.1	42.3%	26	⁸⁹SrCl₂ 4 mci/d, 10 days for a course; ⁹⁹Tc-MDP 5.5 mg/d, intravenously, 5 days for a course	4 cases (pain, leukopenia, thrombocytopenia, allergic reaction, gastrointestinal reaction)
Zhang J Y, et al^[36] 2019	Breast cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	50.48±8.1	100.0%	35	⁸⁹SrCl₂ 48-1.85 MBq/kg.	Fever (2 cases), nausea (1 case), vomiting (1 case), elevated serum creatinine (0 cases), abnormal blood calcium (2 cases), hematotoxicity (6 cases of grade 1, 3 cases of grade 2, and 0 cases of grade 3)
			⁹⁹Tc-MDP+⁸⁹SrCl₂	48.81±8.0		35	⁸⁹SrCl₂ 48-1.85 MBq/kg; ⁹⁹Tc-MDP 11 mg/d, 10 days for a course	Fever (1 case), nausea and vomiting (1 case), elevated serum creatinine (1 case), abnormal blood calcium (3 cases), hematotoxicity (5 cases of grade 1, 2 cases of grade 2, 0 cases of grade 3)
Liu L, et al^[23] 2019	Unspecified	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	56.8±6.7	46.7%	60	⁸⁹SrCl₂ 14.8×10⁷/time	No adverse reaction
Liu L, et al^[23] 2019		Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂	55.9±7.0	43.3%	60	⁸⁹SrCl₂ 14.8×10⁷/time; ⁹⁹Tc-MDP 200 mg/d, 5 days for a course
Liu J G, et al^[22] 2020	Prostate, breast, lung, stomach, and other cancers	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	58.2±12.0	45.9%	37	⁸⁹SrCl₂ 4mci, every 3-6 months	Leukocyte and platelet: 3 patients (with varying degrees), among which 1 patient received radiotherapy before treatment, 1 patient received chemotherapy before treatment, and 1 patient showed mild elevation of alanine aminotransferase in 3-4 weeks, which was reduced to normal after symptomatic treatment
			⁹⁹Tc-MDP	59.3±12.0	48.3%	29	⁹⁹Tc-MDP 22 mg/d, 5 days for a course, once a month, for 2-3 courses	No adverse reaction
			⁹⁹Tc-MDP+⁸⁹SrCl₂	58.9±12.0	48.3%	29	⁹⁹Tc-MDP 22 mg/d, 5 days for a course, once a month, for 2-3 courses; ⁸⁹SrCl₂ 4 mci, every 3 to 6 months	Leukocyte and platelet: 3 patients (with varying degrees), among which 1 patient received radiotherapy before treatment, 1 patient received chemotherapy before treatment, and 1 patient showed mild elevation of alanine aminotransferase in 3-4 weeks, which was reduced to normal after symptomatic treatment
Fu Y J, et al^[17] 2020	Prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁸⁹SrCl₂	68.41±7.2	0.0%	38	⁸⁹SrCl₂ 1.48 MBq/kg	5.26% (2/38): anemic in 1 case; myelosuppression in 1 case
	Prostate cancer	Rate of relief of bone pain and healing of bone metastases	⁹⁹Tc-MDP+⁸⁹SrCl₂	69.04±6.9		39	⁸⁹SrCl₂ 1.48 MBq/kg; ⁹⁹Tc-MDP, 20 days for a course, for 1 course	12.82% (5/39): poor appetite in 2 cases; fatigue in 1 case; phlebitis in 1 case; skin redness and swelling in 1 case

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Outcome	Before exclusion			After exclusion^*
Outcome	RR	95% CI	P value	RR	95% CI	P value
⁹⁹Tc-MDP+⁸⁹SrCl₂ vs ⁸⁹SrCl₂
Bone pain relief rate	1.22	1.18-1.27	<0.001	1.22-1.25	1.17-1.31	<0.001
Bone metastases healing rate	1.35	1.25-1.47	<0.001	1.33-1.42	1.22-1.58	<0.001
Adverse reaction rate	0.83	0.53-1.30	0.42	0.76-0.89	0.47-1.41	0.08-0.59
⁹⁹Tc-MDP vs ⁸⁹SrCl₂
Bone pain relief rate	0.98	0.90-1.06	0.57	0.95-0.99	0.82-1.10	0.40-0.76
Bone metastases healing rate	0.93	0.82-1.06	0.27	0.80-0.97	0.57-1.12	0.19-0.63
Adverse reaction rate	0.93	0.76-1.13	0.45	0.29-0.98	0.10-1.20	0.03-0.82

A meta-analysis of the efficacy of ⁹⁹Tc-MDP alone and in combination with ⁸⁹SrCl₂ in the treatment of bone metastases

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