1 Introduction

Osteoporosis is an age-related silent disease characterized by weakens bones and reduced bone density due to the low level of calcium and vitamin D in the blood.¹³ Osteoporotic patients suffer from the increased risk of fractures and it has been increased at a drastic rate among Iranian population.^9,27 Bone fragility or osteoporosis is common in adults over 50 especially among women because after the age of 30 when bone tissue is not undergoing the process of renewal, bone breakdown overcome the new bone formation.^6,31,32,35 As bones are not renewing they become thinner and more fragile over the passage of time without any noticeable signs of deterioration until a fracture occurs and suffering begins.^4,18,19 All bones of the body are equally affected in osteoporosis but it is particularly common in the weight-bearing bones of the body such as hips, spine and wrists etc.²³ Several medical and lifestyle-related elements in addition to the age are also considered key risk factors for bone fragility such as family history, ethnicity, hormonal deficiency diseases, nutritional deficiency etc.^2,22,34 While osteoporosis may not cause immediate pain, over time it can lead to a variety of serious complications if left unmanaged.¹⁰ Osteoporosis can cause severe damage to hips and vertebrae due to the highest level of fragility and can result in a long-term disability, chronic pain, and in some cases, even death⁷ so the primary goal during the treatment of osteoporosis is to prevent fractures.¹⁶

Recombinant parathyroid hormone (rPTH) has been considered as one of the preferred drug based treatment for the osteoporosis³⁰ as it is an effective way of treatment especially in patients who need concurrent management of both the osteoporosis and any existing fractures.¹⁴ It can also improve bone density and strength, thereby reducing the risk of fractures.²⁶ Unlike traditional osteoporotic treatments such as bisphosphonates, the hormones (estrogen & calcitonin) promotes the formation of new bone tissue.²⁰ The rPTH approach becomes more important in situations where surgical interventions are not feasible, such as cases involving spinal stenosis or in aging patients with persistent comorbidities.^12,29 Considering the significance of these approaches, this study is aimed to evaluate the effectiveness of a locally made rPTH (CinnoPar®, manufactured by CinnaGen Pharmaceutical Co., Iran with a proven therapeutic efficacy) in the treatment of osteoporosis and pain management.

2 Methods and materials

3 Results

3.1

3.1 T-score index for bone mineral density

Bone fragility due to the Osteoporosis is an age-related disease and the mean age of both group was determined to evaluate the efficacy of the drugs. The mean age in the CinnoPar® group was recorded as 68.2 whereas the mean age of the bisphosphonate group was recorded as 67.3. The T-score of the first group before treatment was 2.95, and two years after treatment was recorded as 2.62. The T-score of the second group before treatment was 2.92, while after two years of treatment it was recorded as 2.69 (P>5 %) as shown in Fig. 1.

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Fig. 1 Comparing changes in bone density between CinnoPar® and bisphosphonate treatment groups over two years.

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3.2

3.2 Oswestry Disability Index (ODI) scores

ODI score was calculated to determine the disability level of the patients. It was calculated that 89 patients had severe disability whereas 77 had moderate disability, with none in the mild category. After one-year of treatment severe disability decreased to 63, and these patients were also moved to mild disability. By the end of second year, severe cases dropped to 51, and mild disability increased as shown in Fig. 2 (Chi-square (χ²): 111.47), (p < 0.05).

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Fig. 2 Significant reduction in Oswestry Disability Index Scores over two years of treatment among all patients.

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In CinnoPar® Group, 46 patients were reported with severe disability whereas 37 had moderate, and none had mild disability. After one-year of CinnoPar® treatment, severe disability dropped to 26, and mild disability increased to 39. It was observed that after two years of treatment, only 19 patients remained severely disabled and 45 patients moved to mild disability (p < 0.05) as it has been reported in Fig. 3.

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Fig. 3 Cinnopar group: Odi score distribution over time.

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Disability in the bisphosphonate group was recorded as 43 at severe level whereas 40 patients were reported to had moderate disability with none in mild disability category. After one-year of treatment, severe disability reduced to 37 and only 24 patients had mild disability. After two years, severe disability dropped to 32 and mild disability increased to 38 as described in Fig. 4 (p < 0.05).

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Fig. 4 Bisphosphonate group: Odi score changes over time.

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All groups showed statistically significant improvement in disability scores over the two-year period, with the CinnoPar® group showing a slightly more pronounced effect as compared to the bisphosphonate group which was also considered as a standard group. Table 1 summarizes the values measured by the SF-36 questionnaire before and after treatment. It is clear from the date that the first three parameters of the SF-36 did not show significant changes in either group during the treatment. However, there were significant improvements observed in the last two parameters i.e. social activity and pain, with a p-value of >0.015.

Table 1 Comparison of both groups in the SF-36 questionnaire.

	CinnoPar® Group		Bisphosphonate Group
Scale	Before Treatment	After Treatment	Before Treatment	After Treatment
General Health	85.3 (−/+ 14)	90.2 (−/+ 14)	86.2 (−/+13.5)	91.3 (−/+ 14)
Limitation of Activity	73.1 (−/+ 30.2)	82.1 (−/+ 15.2)	74.2 (−/+ 20.1)	78.1 (−/+ 14.2)
Emotional Health Problem	85 (−/+30.3)	86 (−/+ 28.2)	83 (−/+ 28.2)	87 (−/+ 28.4)
Social Activities	78 (−/+ 19.2)	88 (−/+ 16.5)	78.2 (−/+ 17.3)	82 (−/+ 16.2)
Pain	62.2 (−/+ 13.5)	80.3 (−/+ 17.95)	68.2 (−/+ 19.1)	71.2 (−/+ 14.5)

4 Discussion

Bone fragility is a bone weakening phenomenon happening above the 50 and is basically due to the decline in bone mass and density which is the main cause of fragility fractures especially to the vertebral and spines.¹⁷ Fragility fractures are very serious global health concern as these are increasing at an alarming rate and only in 2019, an increase of 33 % fragility fractures with over 178 million new cases have been reported around the world.³³ Fragility fractures are caused by osteoporosis, a condition of reduced bone density due to the low level of calcium and vitamin D in the blood.¹ Osteoporotic patients frequently experience chronic lower back pain, deteriorating their everyday life and should be treated as soon as possible with minimum side effects.³ Combinatorial approaches using salt and hormone therapies, are considered the gold standards in the treatment of Osteoporotic patients³ which is the main purpose of the current clinical evaluation to investigate the both, clinical efficacy and side effects of CinnoPar®, a locally manufactured teriparatide.

Therapeutic efficacy of several variants of Teriparatide have been evaluated by several clinical experts to treat the osteoporosis. Hwang and colleagues in 2006 performed a comparative evaluation of teriparatide and calcitonin in 63 women diagnosed with stable osteoporosis and found teriparatide more effective in increasing overall bone density than calcitonin (4.5 % vs. 1.1 %).¹¹ In 2008, Miyauchi et al. conducted a study to evaluate the therapeutic efficacy of teriparatide on osteoporosis in postmenopausal Japanese women and found that teriparatide has a positive and stable impact on bone formation.²¹ Recker and colleagues (2009) also conducted a comparative study to evaluate the effects of teriparatide and strontium ranelate on bone turnover markers in postmenopausal women with osteoporosis²⁵ and concluded similar results. All these studies were performed on less than 100 patients with a follow up time of six-months is comparison to the current clinical evaluation which has included over 166 patients with a median age of 65+ and the observations were followed up for two years after the treatment.

Several other studies following the combinatorial therapeutic approaches have also been performed in past decade such as work done by Ellegaard and colleagues in 2010 using parathyroid hormone to treat the osteoporotic patients,⁸ Krege et al., in 2014 who also monitoring the treatment of postmenopausal osteoporosis with teriparatide¹⁵ and Paolucci et al., who evaluated the management of chronic pain in patients with osteoporosis using the teriparatide in 2016.²⁴ In 2017, a study involving 100+ patients with established or early-state osteoporosis who were treated using teriparatide explored the pathophysiology and therapeutic strategies for osteoporosis.⁵ Using CinnoPar® to treat the osteoporatic patients have also been reported by several researchers with a wide range of age of patients and very lower number of treatment subjects²⁸ which led to the designing of the current cohort of short range of age group with higher number of patients. Most interesting study on the efficacy and safety of teriparatide for osteoporosis was performed in 2019 by Minisola et al., who studied 100+ patients with 18 months follow up at a parallel time when the current cohort was going on. Their study was discontinued due to the discontinuation of CinnoPar® making the present cohort, a more reliable answer to the clinical efficacy of CinnoPar® for osteoporosis.

Conducted at a private clinic in Western Tehran, current research work included 180 patients experiencing both lower back pain and osteoporosis. A significant improvement in disability levels (P < 0.05) was observed in the patients who received CinnoPar®. Additionally, the same group showed significant improvements in the social and pain management as per SF-36 questionnaire results presented in Table 1. These findings suggest CinnoPar®, a suitable, effective and non-invasive candidate drug for the treatment for thoracic and lumbar osteoporosis, providing substantial relief from lower back pain with minimal side effects. A possible hypothesis behind this might be the role of CinnoPar® in the repairmen or realignment of the micro-fractures caused by osteoporosis as how this drug is contributing to reduce the lower back pain. However, several limitations impacted the detailed analysis of the current snapshopt, primarily financial constraints that deterred patient participation due to the high cost of the drug. A comprehensive pharmacokinetic study at the cellular and molecular level is required to answer the questions on its molecular mechanism to reduce the pain and improve the bone density and fragility. Future research should prioritize making the medication more affordable, potentially through enhanced insurance coverage and involvement of inter-disciplinary teams to stduy all aspects of the drug mechanism.

5 Conclusion

The current evaluation is a two-years long study of the therapeutic efficacy of CinnoPar®. It has been concluded that despite financial constraints and medication-related adverse effects, CinnoPar® could be an effective non-invasive treatment way for improving the bone fragility of thoracic and lumbar vertebrae in osteoporotic patients with minimal side effects. Significant improvements of Oswestry disability index score and in certain domains of SF-36 questionnaire were observed in CinnoPar® group as compared to bisphosphonates group. Addressing financial barriers and improving the drug's formulation to further minimize the side effects could increase patient accessibility and compliance. Long-term clinical evaluations should be made in future research designs to explore the long-term of use of CinnoPar® as an efficient therapeutic way to treat the back pain and osteoporosis.

CRediT authorship contribution statement

Masoud Mirkazemi: Conceptualization, Methodology, Formal analysis, Investigation, Writing – review & editing, Supervision, All authors checked and approved the final version of the manuscript for publication in the present journal. Behdad Nadimi: Conceptualization, Methodology, Formal analysis, Investigation, Writing – review & editing, All authors checked and approved the final version of the manuscript for publication in the present journal. Parnin Soltani: Methodology, Formal analysis, Investigation, Writing – review & editing, All authors checked and approved the final version of the manuscript for publication in the present journal. Golshan Eslami: Methodology, Formal analysis, Investigation, Writing – review & editing, All authors checked and approved the final version of the manuscript for publication in the present journal. Yasaman Parvisi: Methodology, Formal analysis, Investigation, Writing – review & editing, All authors checked and approved the final version of the manuscript for publication in the present journal. Maryam Garousi: Methodology, Formal analysis, Investigation, Writing – review & editing, All authors checked and approved the final version of the manuscript for publication in the present journal. Azra Izanloo: Methodology, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, All authors checked and approved the final version of the manuscript for publication in the present journal.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethical statement

The current research has been conducted according to the ethical guidelines of the Faculty of Medicine, Tehran Islamic Azad University of Medical Science after the approval by the ethical committee.

Consent for publication

Not applicable.